Tag: Psychedelics

Your brain on shrooms — how psilocybin resets neural networks

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The psychedelic drug causes some lasting changes to the communication pathways that connect distinct brain regions. This heat map shows how patterns of resting brain activity (blue and green) change when psilocybin is taken (red and yellow), then return to normal as the drug wears off. Credit: Sara Moser/Washington University

Taking psilocybin, the hallucinogenic compound found in magic mushrooms, temporarily resets entire networks of neurons in the brain that are responsible for controlling a person’s sense of time and self, finds a study that repeatedly imaged the brains of seven volunteers before, during and after they took a massive dose of the drug.

The findings, published in Nature on 17 July1, could offer insights into why the compound might have a therapeutic effect on some neurological conditions.

Researchers “saw such massive changes induced by psilocybin” that some study participants’ brain-network patterns resembled those of a different person entirely, says Shan Siddiqi, a psychiatric neuroscientist at Harvard School of Medicine in Boston, Massachusetts. “I’ve never seen an effect this strong.”

Most of these changes lasted for a few hours, but one key link between different parts of the brain remained disrupted for weeks.

Psychedelic medicine

Psilocybin is one of several psychedelic drugs, including LSD, ketamine and MDMA (also known as ecstasy), that are being investigated as therapies for conditions such as depression and post-traumatic stress disorder. Despite promising data that have sped treatments towards approval, researchers still don’t fully understand the mechanism that underlies their therapeutic effects.

Many studies have investigated how psychedelics affect individual cells, but Joshua Siegel, a systems neuroscientist at the Washington University School of Medicine in St. Louis, Missouri, took a broader approach to look at how psilocybin affects networks of neurons across the whole brain.

Siegel and his colleagues tracked activity in the brains of seven healthy adults before, during and after they took a high dose of psilocybin. The researchers used functional magnetic resonance imaging (fMRI) to obtain images of blood-flow changes in different parts of the brain — a proxy used to measure how groups of neurons across the brain communicate with one another.

The researchers compared these fMRI scans with images of the same participants’ brains when they did not take any drug or when they took a stimulant. They found that psilocybin caused groups of neurons that normally fire together to become desynchronized. These effects were localized to a group of brain regions called the default mode network, which is usually active when the brain is at ‘wakeful rest’ — for example, during daydreaming — rather than focusing on a task. Although most of the neurons in this network seemed to get back in sync once the acute effects of the drug had worn off, the communication between the default mode network and a brain region called the anterior hippocampus — which is involved in creating our senses of space, time and self — was diminished for weeks.

The researchers also found that a mental exercise called ‘grounding’, which is commonly used in psychedelic therapy to dampen the unpleasant effects of a drug by diverting the recipient’s attention to their surroundings, diminished psilocybin’s effects on the brain. This suggests there could be a neurological signal that grounding techniques can influence, Siegel says.

Deeper insights

Although past experiments have also found that psilocybin disrupts brain networks2,3, this study “provides a deeper resolution and insight into the nature of that disruption”, says Brian Mathur, a systems neuroscientist at the University of Maryland School of Medicine in Baltimore.

The approach was unusual: the researchers homed in on a smaller number of participants than are typically recruited for brain-imaging studies, instead opting to scan each participant about 18 times, creating a mountain of data that the authors could use to support their conclusions.

Mathur cautions that these data cannot show what precisely causes the potential therapeutic benefit of psilocybin — but they offer tantalizing clues. “It’s possible psilocybin is directly causing” the brain-network changes, he says — or perhaps it is creating a psychedelic experience that in turn causes parts of the brain to behave differently, he says.

Siddiqi agrees, adding that it will be useful to untangle whether psilocybin’s blood-flow changes in the brain, which is measured by fMRI, or its direct effects on neurons — or both — are responsible for the brain-network disruptions. Siegel hopes to conduct further experiments to investigate the effects of psilocybin on the brains of people with conditions such as depression.

“The best part of this work is that it’s going to provide a means forward for the field to develop further hypotheses that can and should be tested,” Mathur says.

doi: https://doi.org/10.1038/d41586-024-02275-y

https://www.nature.com/articles/d41586-024-02275-y?utm_source=Live+Audience&utm_campaign=1512a0e984-nature-briefing-daily-20240718&utm_medium=email&utm_term=0_b27a691814-1512a0e984-50113660

Should psychedelics be declassified in order to examine their therapeutic potential in some forms of mental illness?

On By A.P.In Anxiety, Depression, Drugs, hallucinogen, LSD, lysergic acid diethylamaide, MDMA (Ecstasy), Medicine, Neuropsychiatric Disease, PsychosisLeave a comment

Psychedelics were highly popular hallucinogenic substances used for recreational purposes back in the 1950s and 1960s. They were also widely used for medical research looking into their beneficial impact on several psychiatric disorders, including anxiety and depression. In 1967, however, they were classified as a Class A, Schedule I substance and considered to be among the most dangerous drugs with no recognized clinical importance. The use of psychedelics has since been prohibited.

Psychiatrist and honorary lecturer at the Institute of Psychiatry, Psychology and Neuroscience, at Psychiatrist and honorary lecturer at the Institute of Psychiatry, Psychology and Neuroscience, at King’s College London, James Rucker, MRCPsych, is proposing to reclassify and improve access to psychedelics in order to conduct more research on their therapeutic benefits. He believes in the potential of psychedelics so much that late last month he took to the pages of the prestigious journal the BMJ to make his case. He wrote that psychedelics should instead be considered Schedule II substances which would allow a “comprehensive, evidence based assessment of their therapeutic potential.”

“The Western world is facing an epidemic of mental health problems with few novel therapeutic prospects on the horizon,” Rucker told Psychiatry Advisor, justifying why studying psychedelics for treating psychiatric illnesses is so important.

Rucker recognizes that the illicit substance may be harmful to some people, especially when used in a recreational and uncontrolled context. He cited anecdotal reports of the substance’s disabling symptoms, such as long-term emotionally charged flashbacks. However, he also believes that psychedelic drugs can have positive outcomes in other respects.

“The problem at the moment,” he argued, “is that we don’t know who would benefit and who wouldn’t. The law does a good job of preventing us from finding out.”

From a biological perspective, psychedelics act as an agonist, a substance that combines with a receptor and initiates a physiological response to a subtype of serotonin known as 5HT2a. According to Rucker, this process influences the balance between inhibitory and excitatory neurotransmitters.

“The psychedelics may invoke a temporary state of neural plasticity within the brain, as a result of which the person may experience changes in sensory perception, thought processing and self-awareness,” Rucker speculated. He added that psychedelic drugs can act as a catalyst that stirs up the mind to elicit insights into unwanted cycles of feelings, thoughts and behaviors.

“These cycles can then be faced, expressed, explored, interpreted, accepted and finally integrated back into the person’s psyche with the therapist’s help,” he explained. Reclassifying psychedelics could mean that the mechanism by which these substances can help with anxiety, depression and psychiatric symptoms could be studied and understood better.

Several experts in the field of drug misuse have disagreed strongly with Rucker’s proposals in this area, and are quick to refute his findings and recommendations. Nora Volkow, MD, director of the National Institute on Drug Abuse (NIDA), emphasized the fact that psychedelics can distort a person’s perception of time, motion, colors, sounds and self. “These drugs can disrupt a person’s ability to think and communicate rationally, or even to recognize reality, sometimes resulting in bizarre or dangerous behavior,” she wrote on a NIDA webpage dealing with hallucinogens and dissociative drugs.

“Hallucinogenic drugs are associated with psychotic-like episodes that can occur long after a person has taken the drug,” she added. Volkow also says that, despite being classified as a Schedule I substance, the development of new hallucinogens for recreational purposes remains of particular concern.

Rucker has several suggestions to help mediate the therapeutic action of the drug during medical trials, and thereby sets out to rebut the concerns of experts such as Volkow. When a person is administered a hallucinogen, they experience a changed mental state. During that changed state, Rucker points out, it is possible to control what he describes as a “context,” and thereby make use of the drug more safe.

According to Rucker, the term “context” is divided into the “set” and the “setting” of the drug experience. “By ‘set,’ I mean the mindset of the individual and by ‘setting’ I mean the environment surrounding the individual,” he explained.

To prepare the mindset of the person, Rucker said that a high level of trust between patient and therapist is essential. “A good therapeutic relationship should be established beforehand, and the patient should be prepared for the nature of the psychedelic experience,” he suggested. The ‘setting’ of the drug experience should also be kept closely controlled — safe, comfortable and low in stress.

It is also necessary to screen participants who undergo the drug experience in order to minimize the risk of adverse effects. Rucker suggested screening patients with an established history of severe mental illness, as well as those at high risk of such problems developing. It is also important to screen the medical and drug history of participants.

“The action of psychedelics is changed by many antidepressant and antipsychotic drugs and some medications that are available over the counter, so a full medical assessment prior to their use is essential,” he said.

In order to avoid the danger of addiction, psychedelics should be given at most on a weekly basis. Indeed, for many patients, very few treatments should be required. “The patient may need only one or two sessions to experience lasting benefits, so the course should always be tailored to the individual,” Rucker advised.

If there are any adverse effects during the psychedelic experience, a pharmacological antagonist or antidote to the drug can be administered to immediately terminate the experience. “This underlines the importance of medical supervision being available at all times,” Rucker noted.

Psychedelics are heavily influenced by the environment surrounding the drug experience. Rucker is proposing they be administered under a controlled setting and with a trusted therapist’s supervision. Together with a reclassification of the drug, medical research could generate a better understanding and application of the benefits of psychedelics to mental health.

1.Rucker JJH. Psychedelic drugs should be legally reclassified so that researchers can investigate their therapeutic potential. BMJ. 2015; 350:h2902.

http://www.bmj.com/content/350/bmj.h2902/related