Research helps provide scientific framework for psilocybin use in therapeutic settings

April 11, 2022

Science Daily/Oregon State University

A new paper by an Oregon State University-led research team provides a scientific framework to help shape the rollout of a program in Oregon that will legally permit the use of psilocybin for therapeutic reasons.

Oregon voters approved a ballot measure in 2020 to allow use of psilocybin, the hallucinogenic compound found in some magic mushrooms, in therapeutic settings, becoming the first state to do so. Preliminary clinical trial data has shown psilocybin has potential to address mental health issues including depression, anxiety and PTSD.

The state created an advisory board to recommend how to roll out a safe and equitable system for psilocybin use. The Oregon Health Authority in February released draft rules crafted by the advisory board. They are expected to be finalized in the next year.

Jessie Uehling, a mycologist at Oregon State University who studies fungi and their applications that benefit humanity, was appointed last year by Gov. Kate Brown to the advisory board. Her involvement with the board made her realize the need for the recently published paper in the journal Fungal Biology.

"There was not a synthesis of all the information about psilocybin that an entity like the advisory board or any other state- or federal-level group would need to make decisions that are informed by science," said Uehling, an assistant professor who has a doctoral degree in genetics and genomics and a master's in mycology.

She, along with researchers in Mexico and several universities in the U.S., set out to change that. The paper they just published provides an overview of the biology, diversity and history of psilocybin-containing fungi.

The authors detail that there are hundreds of fungal species belonging to at least seven genera that are capable of producing psilocybin. Further, they discuss how many psilocybin-producing fungi have deadly poisonous lookalikes which grow in similar locations in natural habitats.

They also focus on how Indigenous people around the world have historically used the compound for sacred traditions in part because they say these cross-disciplinary insights need to be published, citable and publicly available.

While indirect evidence of hallucinogenic mushroom rituals dates back thousands of years in Northern Africa and Spain; its use, for hundreds of years, still persists in Mexico. Rules governing how these mushrooms are used among Indigenous Mexican groups has resulted in safe consumption for centuries, the researchers note. These rules include being guided by an elder or shaman, not mixing alcohol, medicine or drugs and discouraging travel for a week after the ceremony.

"These mushrooms and their traditions constitute a unique biocultural heritage whose use by Western society must be based on their respect and conservation," said Roberto Garibay-Orijel, a researcher at the Universidad Nacional Autónoma de México and co-author of the paper.

He said it's important that the paper emphasizes that the species of mushroom only found in Mexico, and strains from Indigenous territories in Mexico, are protected by the Nagoya protocol, an international agreement that prohibits their use for commercial purposes without the consent of their ancestral owners.

Recent Western, medicalized psilocybin trials have been designed to mirror the guided experience used by Indigenous groups. The trials have confirmed the importance of preparation and setting when using psilocybin-producing fungi.

There are currently more than 60 psilocybin clinical trials overseen by the National Institutes of Health. Preliminary data suggest psilocybin therapies are effective in treating major depressive disorder, obsessive-compulsive disorder, smoking cessation and alcoholism.

Results of psilocybin ingestion outside of clinical trials have found an increased connection to nature, enhanced creativity, greater enjoyment of music and increased positive mood.

Meanwhile, cities across the U.S. are decriminalizing psilocybin and Washington is considering a measure similar to Oregon's that would legalize psilocybin for therapeutic reasons.

"Society is having this moment right now where fungi are being appreciated for being really cool," Uehling said. "But they are also really powerful and some can be deadly. So we really need to better understand them through scientific research and proceed with safety as a first priority."

https://www.sciencedaily.com/releases/2022/04/220411101254.htm

Babies exposed to cannabis in the womb may be at risk for obesity, high blood sugar

Both CBD and THC put children at risk despite CBD being marketed as having health benefits

March 31, 2022

Science Daily/The Endocrine Society

Cannabis use among pregnant women is on the rise and may be associated with negative health outcomes in children, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology and Metabolism.

A 2016 study in Colorado revealed that up to 22% of pregnant women had detectable levels of cannabinoids in their body. Women who use cannabis, both tetrahydrocannabinol (THC) and cannabidiol (CBD), during pregnancy could be putting their child at risk for low birth weight and behavioral problems. Exposure to cannabinoids may also increase the child's future risk of obesity and high blood sugar.

Part of CBD's popularity is that it is marketing as being "nonpsychoactive," and that consumers can reap health benefits from the plant without the high. CBD is advertised as providing relief for anxiety, depression and post-traumatic stress disorder. It is also marketed to promote sleep.

"We found that cannabis use during pregnancy was linked to increased fat mass percentage and fasting glucose levels in 5-year-old children," said Brianna Moore, Ph.D., of the Colorado School of Public Health in Aurora, Colo. "We would encourage women to refrain from using any cannabis while pregnant or breastfeeding to minimize adverse health effects in the offspring."

The researchers studied urine samples from 103 pregnant women, 15% of whom had detectable levels of cannabinoids (such as THC and CBD) in their urine. These mothers' 5-year-old children had higher fat mass and fasting glucose levels compared to children who were not exposed to cannabis during pregnancy.

"More studies are needed to understand how exposure to different cannabinoids during pregnancy may impact the offspring," Moore said.

https://www.sciencedaily.com/releases/2022/03/220331101458.htm

New study explores relationship between psychedelics and consciousness

March 31, 2022

Science Daily/Johns Hopkins Medicine

Psychedelic drugs, like psilocybin, an ingredient found in so-called magic mushrooms, have shown promise in treating a range of addictions and mental health disorders. Yet, there's something mysterious and almost mystical about their effects, and they are commonly believed to provide unique insights into the nature of consciousness.

Now, a new study by Johns Hopkins Medicine researchers addresses the question of whether psychedelics might change the attribution of consciousness to a range of living and nonliving things.

The findings, published March 28 in Frontiers in Psychology, reveal that higher ratings of mystical type experiences, which often include a sense that everything is alive, were associated with greater increases in the attribution of consciousness.

"This study demonstrates that when beliefs change following a psychedelic experience, attributions of consciousness to various entities tend to increase," says Sandeep Nayak, M.D., postdoctoral research fellow at the Johns Hopkins Center for Psychedelic and Consciousness Research and one of the researchers involved in the study. "It's not clear why, whether that might be an innate drug effect, cultural factors or whether psychedelics might somehow expose innate cognitive biases that attribute features of the mind to the world."

For the study, the researchers analyzed data gathered between August 2020 and January 2021 on 1,606 people who have had a belief-changing psychedelic experience. Participants averaged 35 years of age and were predominately white (89%), male (67%) and from the United States (69%).

Study participants completed an internet-based survey that included questions focused on belief changes attributed to a single psychedelic experience with a classic psychedelic substance (e.g., psilocybin mushrooms, LSD, ayahuasca). The survey also included questions about demographics, psychedelic use, personality, and scientific knowledge and attitudes.

The study found that among people who have had a single psychedelic experience that altered their beliefs in some way, there were large increases in attribution of consciousness to a range of animate and inanimate things. For example, from before to after the experience, attribution of consciousness to insects grew from 33% to 57%, to fungi from 21% to 56%, to plants from 26% to 61%, to inanimate natural objects from 8% to 26% and to inanimate manmade objects from 3% to 15%.

"On average, participants indicated the belief-changing experience in question occurred eight years prior to taking the survey, so these belief changes may be long-lasting," says Nayak.

Classic psychedelics -- the pharmacological class of compounds that includes psilocybin and LSD -- produce visual and auditory illusions and profound changes in consciousness, altering a person's awareness of their surroundings and of their thoughts and feelings. These substances produce unusual and compelling changes in conscious experience, which have prompted some to propose that psychedelics may provide unique insights into the nature of consciousness itself.

"The results suggesting that a single psychedelic experience can produce a broad increase in attribution of consciousness to other things, raises intriguing questions about possible innate or experiential mechanisms underlying such belief changes," says Roland Griffiths, Ph.D., the Oliver Lee McCabe III, Ph.D., Professor in the Neuropsychopharmacology of Consciousness at the Johns Hopkins University School of Medicine, and founding director of the Johns Hopkins Center for Psychedelic and Consciousness Research. "The topic of consciousness is a notoriously difficult scientific problem that has led many to conclude it is not solvable."

https://www.sciencedaily.com/releases/2022/03/220331134240.htm

Exploring the therapeutic uses of ketamine

The drug could be a game changer in the treatment of mental illness

March 18, 2022

Science Daily/University of British Columbia Okanagan campus

First manufactured more than 50 years ago, ketamine is a fast-acting dissociative anesthetic often used in veterinary and emergency medicine. Ketamine also has a history of being an illicit party drug.

Now, ketamine is getting a closer look.

Researchers from UBC Okanagan and the University of Exeter have identified ketamine as a potentially powerful tool in the fight against mental illness.

In a recent study published in the British Journal of Psychiatry, the research team found ketamine to have significant anti-depressant and anti-suicidal effects. They also found evidence that suggests its benefits don't stop there.

Led by Psychology Professor Dr. Zach Walsh and doctoral student Joey Rootman -- both based in the Irving K. Barber Faculty of Arts and Social Sciences -- the research team arrived at this conclusion after analyzing more than 150 worldwide studies on the effects of sub-anesthetic ketamine doses for the treatment of mental illness. The study was co-led by Professor Celia Morgan and doctoral student Merve Mollaahmetoglu from the University of Exeter in the United Kingdom.

"We found strong evidence that indicates ketamine provides rapid and robust anti-depressant and anti-suicidal effects, but the effects were relatively short-lived," explains Rootman. "However, repeated dosing appeared to have the potential to increase the duration of positive effects."

Beyond these results, the study provides evidence that suggests ketamine may be helpful in the treatment of other disorders, including eating disorders, problematic substance use, post-traumatic stress and anxiety -- though the evidence in these areas is scarce.

"What our research provides is an up-to-date overview and synthesis of where the knowledge on ketamine is at right now," explains Rootman. "Our results signal that ketamine may indeed have a broader spectrum of potential applications in psychiatric treatment -- and that tells us that more investigation is needed."

This study serves as a foundation for fellow researchers looking to design ketamine-related projects and offers valuable data for clinicians considering using ketamine with their patients.

The results also help to satisfy the public's appetite for information on innovative and emerging psychiatric treatments, says Dr. Walsh, explaining the review provides a relatively compact document with evidence regarding which ketamine treatments may be helpful for diverse diagnoses.

"As many as one in five Canadians will experience a mental illness this year, and the reality is that existing treatments don't work for everyone," he says. "As a result, many Canadians are curious about new approaches to help with these serious conditions."

Overall, while Dr. Walsh acknowledges research into other treatment areas is just beginning, he finds the preliminary evidence encouraging.

"We need a lot more information on how these interventions could work -- for example, administering the drug is only a part of treatment. We need to figure out what amount and type of psychotherapy would best compliment the drug intervention to really maximize potential benefits," he explains. "With that being said, it is a truly exciting time for ketamine research. If it can deliver the relief that early evidence suggests it can, this could be among the most significant developments in mental health treatment in decades."

https://www.sciencedaily.com/releases/2022/03/220318161446.htm

Little evidence on how psilocybin therapy interacts with existing psychiatric treatments, review finds

Review comes as Oregon embarks on voter-approved initiative to legalize psilocybin services in 2023

March 18, 2022

Science Daily/Oregon Health & Science University

As Oregon embarks on a voter-approved initiative to permit psychoactive mushrooms in clinical use, a new systematic evidence review from Oregon Health & Science University reveals a lack of scientific research describing the interactions between widely used psychiatric medications and psychedelics like psilocybin and MDMA.

The scarcity of data is problematic for people believed to benefit most from psychedelics: those with mental health conditions such as depression, anxiety and post-traumatic stress disorder.

The review was published last week in the journal Psychopharmacology.

"There's a huge deficit in the scientific literature," said lead author Aryan Sarparast, M.D., assistant professor of psychiatry in the OHSU School of Medicine. "There's a major incongruence between the public enthusiasm and exuberance with psychedelic substances for mental health issues -- and what happens when they combine with the existing mental health treatments that we have now."

The researchers decided to conduct the evidence review because they wanted to learn more about interactions between widely prescribed medications such as antidepressants and psychedelics, including MDMA and psilocybin, known colloquially as magic mushrooms.

They found a total of 40 studies dating back to 1958, including 26 from randomized controlled studies, 11 case reports and three epidemiologic studies.

Researchers found only one study that examined how psilocybin interacts with antidepressant medications. Further, Sarparast noted that all of the clinical trials were conducted with healthy volunteers who were administered a psychiatric medication and a psychedelic at the same time -- a clear sign of the need for further research on the clinical outcomes of combining pharmaceutical medications with psilocybin.

Sarparast said he is concerned that the lack of evidence will lead many providers to direct patients to taper off existing medications before being offered clinical psilocybin therapy. Oregon regulators are currently in the process of developing rules to permit the clinical use of psilocybin products and services beginning Jan. 2, 2023.

Patients with mental health conditions may well benefit from psilocybin therapy, but Sarparast said he worries about the implications of stopping existing psychiatric treatment in order to receive psilocybin services. This may force vulnerable people into choosing between their existing medical treatment or psilocybin services.

"That's a very, very tough place to be," Sarparast said.

There's a considerable amount of important data not captured in a literature review related to real-world use, noted co-author Christopher Stauffer, M.D., assistant professor of psychiatry in the OHSU School of Medicine and a physician-scientist at the VA Portland Health Care System.

"Psilocybin has been around in Western society since the late 1950s, before many of our psychiatric medications have existed," Stauffer said. "Nonetheless, people attempting to navigate Oregon's psilocybin services in the context of ongoing psychiatric treatment should work closely with knowledgeable professionals."

https://www.sciencedaily.com/releases/2022/03/220318131632.htm

Marijuana for medical use may result in rapid onset of cannabis use disorder

The hype over medical marijuana for treating health problems may be exaggerated, researchers find.

March 18, 2022

Science Daily/Massachusetts General Hospital

A new study shows that using cannabis products to treat pain, anxiety and depression failed to improve these symptoms while doubling the risk of developing the addictive symptoms of cannabis use disorder. People seeking cannabis to treat symptoms of anxiety and depression were at greatest risk of CUD. Contrary to evidence-based medicine, people with medical marijuana cards choose their own products and dosing, suggesting the need for better controls over dispensing, use, and professional follow-up of these patients.

Obtaining a medical marijuana card (MMC) to use cannabis products to treat pain, anxiety, or depression symptoms led to the onset of cannabis use disorder (CUD) in a significant minority of individuals while failing to improve their symptoms, according to a study by Massachusetts General Hospital (MGH) researchers and published in JAMA Network Open. Researchers found that individuals at greatest risk of developing the addictive symptoms of CUD were those seeking relief from anxiety and depression, suggesting the need for stronger safeguards over the dispensing, use, and professional follow-up of people who legally obtain cannabis through MMCs.

"There have been many claims about the benefits of medical marijuana for treating pain, insomnia, anxiety and depression, without sound scientific evidence to support them," says lead author Jodi Gilman, PhD, with the Center for Addiction Medicine at MGH. "In this first study of patients randomized to obtain medical marijuana cards, we learned there can be negative consequences to using cannabis for medical purposes. People with pain, anxiety or depression symptoms failed to report any improvements, though those with insomnia experienced improved sleep." Particularly disturbing to Gilman was the fact individuals with symptoms of anxiety or depression -- the most common conditions for which medical cannabis is sought -- were most vulnerable to developing cannabis use disorder. CUD symptoms include the need for more cannabis to overcome drug tolerance, and continued use despite physical or psychological problems caused by the cannabis."

"Medical" cannabis has surged in popularity as 36 states and the District of Columbia have commercialized its use (as of December 2021) for myriad health conditions through medical marijuana cards. These cards require written approval of a licensed physician who, under the current system, is typically not the patient's primary care provider but a "cannabis doctor" who may provide authorization to patients with only a cursory examination, no recommendations for alternative treatments, and no follow-up. Indeed, the medical marijuana industry functions outside regulatory standards that apply to most fields of medicine.

MGH researchers began their trial in 2017 with 269 adults (average age of 37) from the greater Boston area who were interested in obtaining a medical marijuana card. One group was allowed to get MMCs immediately, while the second group, designed to serve as a control, was asked to wait 12 weeks before obtaining a card. Both groups were tracked over 12 weeks. The team found that the odds of developing CUD were nearly two times higher in the MMC cohort than in the wait list control group, and that by week 12, 10 percent of the MMC group had developed a CUD diagnosis, with the number rising to 20 percent in those seeking a card for anxiety or depression.

"Our study underscores the need for better decision-making about whether to begin to use cannabis for specific medical complaints, particularly mood and anxiety disorders, which are associated with an increased risk of cannabis use disorder," says Gilman. Regardless of the specific health condition for which cannabis is sought, Gilman believes that regulation and distribution of cannabis to people with medical marijuana cards must be greatly improved. "There needs to be better guidance to patients around a system that currently allows them to choose their own products, decide their own dosing, and often receive no professional follow-up care."

https://www.sciencedaily.com/releases/2022/03/220318110249.htm

Do 'behavioral psychedelics' help patients make lasting, positive change?

March 16, 2022

Science Daily/University of California - Los Angeles Health Sciences

Psychedelics may find new, legitimate roles in treatment for anxiety, depression, stress disorders, addiction, and other mental and behavioral health problems. But ensuring they do requires developing rigorous, standardized methods to study and apply the results, according to a new report.

Despite their reputation as illicit drugs, psychedelics may find new, legitimate roles in treatment for anxiety, depression, stress disorders, addiction, and other mental and behavioral health problems. But ensuring they do requires developing rigorous, standardized methods to study and apply the results, according to a new report.

In a perspective published in Frontiers in Psychiatry, researchers from UCLA Health and Harvard Medical School coin the term "behavioral psychedelics" -- "the study of psychedelics to foster intentional changes in habits and behaviors to improve health and resilience."

"Changing human behavior may sound simple but is exceedingly difficult, especially for behaviors that arise from years of thinking and acting in relatively rigid, routinized ways," write the authors, George Slavich, PhD, professor of psychiatry and behavioral sciences at UCLA and research scientist at the UCLA Semel Institute for Neuroscience and Human Behavior, and Edmund Neuhaus, PhD, assistant professor of psychology at Harvard. "One emerging strategy for accomplishing behavior change involves using psychedelic compounds to make the mind more malleable and open."

According to the authors, "psychedelics-assisted psychotherapy" may provide many health benefits and even cost savings, but the current therapeutic approach is poorly targeted.

"Looking forward, we believe that further refinement is needed to operationalize and test [the] components to establish a best-practice standard of care for treating psychiatric, addiction, somatic, and behavioral health problems," they said.

The authors say their behavioral psychedelics concept is intended to develop "targeted approaches for therapeutic change that help people achieve enduring functional improvements in self-care, social connection, and family, school, and community responsibilities to help them live the life they desire."

"Psychedelic compounds have the potential to turbocharge the process of transforming the mind, and the race to realize their benefits is in full swing. To maximize these benefits, we believe this work should include behavior as a treatment target with measurable treatment metrics to establish best practices and guidelines," Slavich and Neuhaus write.

https://www.sciencedaily.com/releases/2022/03/220316173309.htm

Largest ever psychedelics study maps changes of conscious awareness to neurotransmitter systems

March 16, 2022

Science Daily/McGill University

Psychedelics are now a rapidly growing area of neuroscience and clinical research, one that may produce much-needed new therapies for disorders such as depression and schizophrenia. Yet there is still a lot to know about how these drug agents alter states of consciousness.

In the world's largest study on psychedelics and the brain, a team of researchers from The Neuro (Montreal Neurological Institute-Hospital) and Department of Biomedical Engineering of McGill University, the Broad Institute at Harvard/MIT, SUNY Downstate Health Sciences University, and Mila -- Quebec Artificial Intelligence Institute have shown how drug-induced changes in subjective awareness are anatomically rooted in specific neurotransmitter receptor systems.

The researchers gathered 6,850 testimonials from people who took a range of 27 different psychedelic drugs. In a first-of-its-kind approach, they designed a machine learning strategy to extract commonly used words from the testimonials and link them with the neurotransmitter receptors that likely induced them. The interdisciplinary team could then associate the subjective experiences with brain regions where the receptor combinations are most commonly found -- these turned out to be the lowest and some of the deepest layers of the brain's information processing layers.

Using thousands of gene transcription probes, the team created a 3D map of the brain receptors and the subjective experiences linked to them, across the whole brain. While psychedelic experience is known to vary widely from person to person, the large testimonial dataset allowed the team to characterize coherent states of conscious experiences with receptors and brain regions across individuals. This supports the theory that new hallucinogenic drug compounds can be designed to reliably create desired mental states.

For example, a promising effect of some psychedelics for psychiatric intervention is ego-dissolution -- the feeling of being detached with the self. The study found that this feeling was most associated with the receptor serotonin 5-HT2A. However, other serotonin receptors (5-HT2C, 5-HT1A, 5-HT2B), adrenergic receptors Alpha-2A and Beta-2, as well as the D2 receptor were also linked with the feeling of ego-dissolution. A drug targeting these receptors may be able to reliably create this feeling in patients whom clinicians believe might benefit from it.

"Hallucinogenic drugs may very well turn out to be the next big thing to improve clinical care of major mental health conditions," says Professor Danilo Bzdok, the study's lead author "Our study provides a first step, a proof of principle that we may be able to build machine learning systems in the future that can accurately predict which neurotransmitter receptor combinations need to be stimulated to induce a specific state of conscious experience in a given person."

This study, published in the journal Science Advances on March 16, 2022, was funded with the help of the Brain Canada Foundation, through the Canada Brain Research Fund, as well as by NIH grant R01AG068563A and the Canadian Institutes of Health Research. Danilo Bzdok was also supported by the Healthy Brains Healthy Lives initiative (Canada First Research Excellence fund), and by the CIFAR Artificial Intelligence Chairs program (Canada Institute for Advanced Research), as well as Google.

https://www.sciencedaily.com/releases/2022/03/220316145736.htm

Brain stimulation shows promise as treatment for cannabis use disorder in people with schizophrenia

Repetitive transcranial magnetic stimulation (rTMS) associated with up to 60 per cent reduction in cannabis use in clinical trial

March 3, 2022

Centre for Addiction and Mental Health

Repetitive transcranial magnetic stimulation (rTMS) was associated with a reduction in self-reported cannabis use by up to 60 per cent among people with schizophrenia who have cannabis use disorder (CUD), according to a CAMH-led study just published in the journal NPJ Schizophrenia.

The double-blind study is the first of its kind to investigate the effectiveness of rTMS in treating CUD in people with schizophrenia, and was supported by the U.S. National Institute on Drug Abuse (NIDA) and the CAMH Foundation.

"People with schizophrenia have very high rates of cannabis use disorder compared to the general population, and there is strong evidence that cannabis use worsens psychiatric symptoms and quality of life in these people," said senior author CAMH clinician scientist Dr. Tony George. "Despite the known harmful effects, there is currently no approved treatment for CUD with or without schizophrenia. These results indicate rTMS may be a safe and effective way to reduce cannabis among people with schizophrenia."

Until relatively recently, brain stimulation technologies like rTMS were used primarily for treatment-resistant depression. However, studies have now found rTMS to be effective in reducing drug use and cravings for several substance use disorders in the general population.

Study participants were given rTMS treatment at the Temerty Centre for Therapeutic Brain Intervention at CAMH five times a week for four weeks targeting the brain's the dorsolateral prefrontal cortex (DLPFC), which is associated with the brain's reward system and executive function.

Those who were given rTMS reported a reduction in cannabis use by up to 60 per cent after 28 days as well as reduced cravings, compared to controls receiving sham rTMS.

The authors state that one of the reasons there is currently no effective treatment for CUD in people with schizophrenia is that people with schizophrenia or other mental illnesses are usually excluded from CUD clinical trials. Dr. George says that CAMH is uniquely positioned to do this kind of research:

"In addition to our ability to conduct clinical trials with brain stimulation at the Temerty Centre, CAMH also has one of the largest schizophrenia outpatient clinics in North America as well as state-of-the-art addiction treatment programs," said Dr. George. "All those factors make CAMH one of the few places in the world that can lead a study like this."

"It was a difficult study to recruit for given the intensity of time commitment required by patients," said study lead author Dr. Karolina Kozak Bidzinski. "However, the awareness patients had of the negative effects cannabis was having on their lives, the expected benefits of reducing their use and noticing the various positive outcomes that would surface throughout the duration of the trial, enabled such a high number of patients to complete the study. Hopefully this work paves the way for more research into investigating the effects of rTMS as a treatment for cannabis use disorder in people with schizophrenia."

https://www.sciencedaily.com/releases/2022/03/220303144146.htm

Psilocybin treatment for major depression effective for up to a year for most patients

February 15, 2022

Science Daily/Johns Hopkins Medicine

Previous studies by Johns Hopkins Medicine researchers showed that psychedelic treatment with psilocybin relieved major depressive disorder symptoms in adults for up to a month. Now, in a follow-up study of those participants, the researchers report that the substantial antidepressant effects of psilocybin-assisted therapy, given with supportive psychotherapy, may last at least a year for some patients.

A report on the new study was published on Feb. 15, 2022 in the Journal of Psychopharmacology.

"Our findings add to evidence that, under carefully controlled conditions, this is a promising therapeutic approach that can lead to significant and durable improvements in depression," says Natalie Gukasyan, M.D., assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. She cautions, however, that "the results we see are in a research setting and require quite a lot of preparation and structured support from trained clinicians and therapists, and people should not attempt to try it on their own."

Over the last 20 years, there has been a growing renaissance of research with classic psychedelics -- the pharmacological class of compounds that include psilocybin, an ingredient found in so-called magic mushrooms. According to the National Institute on Drug Abuse, psilocybin can produce perceptual changes, altering a person's awareness of their surroundings and of their thoughts and feelings. Treatment with psilocybin has shown promise in research settings for treating a range of mental health disorders and addictions.

For this study, the researchers recruited 27 participants with a long-term history of depression, most of whom had been experiencing depressive symptoms for approximately two years before recruitment. The average age of participants was 40, 19 were women, and 25 identified as white, one as African American and one as Asian. Eighty-eight percent of the participants had previously been treated with standard antidepressant medications, and 58% reported using antidepressants in their current depressive episodes.

After screening, participants were randomized into one of two groups in which they received the intervention either immediately, or after an eight-week waiting period. At the time of treatment, all participants were provided with six to eight hours of preparatory meetings with two treatment facilitators. Following preparation, participants received two doses of psilocybin, given approximately two weeks apart between August 2017 and April 2019 at the Behavioral Biology Research Center at Johns Hopkins Bayview Medical Center. Participants returned for follow-up one day and one week after each session, and then at one, three, six and 12 months following the second session; 24 participants completed both psilocybin sessions and all follow-up assessment visits.

The researchers reported that psilocybin treatment in both groups produced large decreases in depression, and that depression severity remained low one, three, six and 12 months after treatment. Depressive symptoms were measured before and after treatment using the GRID-Hamilton Depression Rating Scale, a standard depression assessment tool, in which a score of 24 or more indicates severe depression, 17-23 moderate depression, 8-16 mild depression and 7 or less no depression. For most participants, scores for the overall treatment decreased from 22.8 at pretreatment to 8.7 at one week, 8.9 at four weeks, 9.3 at three months, 7 at six months and 7.7 at 12 months after treatment. Participants had stable rates of response to the treatment and remission of symptoms throughout the follow-up period, with 75% response and 58% remission at 12 months.

"Psilocybin not only produces significant and immediate effects, it also has a long duration, which suggests that it may be a uniquely useful new treatment for depression," says Roland Griffiths, Ph.D., the Oliver Lee McCabe III, Ph.D., Professor in the Neuropsychopharmacology of Consciousness at the Johns Hopkins University School of Medicine, and founding director of the Johns Hopkins Center for Psychedelic and Consciousness Research. "Compared to standard antidepressants, which must be taken for long stretches of time, psilocybin has the potential to enduringly relieve the symptoms of depression with one or two treatments."

The researchers emphasize that further research is needed to explore the possibility that the efficacy of psilocybin treatment may be substantially longer than 12 months. Johns Hopkins is one of the sites of a national multisite randomized, placebo-controlled trial of psilocybin for major depressive disorder.

https://www.sciencedaily.com/releases/2022/02/220215090157.htm

How does cannabis use affect brain health? Caution advised, more research needed, experts say

American Heart Association Scientific Statement

February 10, 2022
Science Daily/American Heart Association

Despite the perception that marijuana is harmless, there is some scientific evidence challenging that belief, and there are many unanswered questions about its impact on brain health, according to a new American Heart Association scientific statement published today in the Association's journal Stroke. This scientific statement will be presented and discussed during a symposium at the Association's International Stroke Conference in New Orleans, today at 7 a.m. CT/ 8 a.m. ET. An American Heart Association scientific statement is an expert analysis of current research and may inform future clinical practice guidelines.

"There's a lot of uncertainty in the medical community about the health effects of marijuana. This scientific statement is intended to guide health care professionals in having a balanced and intentional discussion with patients about the potential known and unknown effects of marijuana on brain health," said writing group Chair Fernando D. Testai, M.D., Ph.D., FAHA, a professor of neurology and rehabilitation at the University of Illinois at Chicago.

This is the Association's first scientific statement on cannabis and brain health, following a statement on marijuana and cardiovascular health, published in August 2020. Both statements are important since marijuana use in the U.S. is increasing, particularly among adolescents and young adults, with about one-third of 12thgraders and nearly half of college students reporting marijuana use in 2018. In addition, the use of marijuana medicinally and/or recreationally has been legalized or decriminalized in many states across the U.S. in the past 2 decades, and the concentration of tetrahydrocannabinol (THC, the psychoactive component in marijuana) in cannabis products has increased significantly, from about 4% in 1995 to 15% in 2018.

The most studied chemicals in cannabis are THC and CBD. THC is the compound in marijuana that gives the sensation of being high. CBD (cannabidiol) has antioxidant and anti-inflammatory properties but does not have psychoactive effects. The potential therapeutic benefits of CBD continue to be investigated in clinical trials.

The U.S. Drug Enforcement Agency (DEA) and the Food and Drug Administration (FDA) classify cannabis as a Schedule I controlled substance, on par with heroin and LSD, for having a "high potential for abuse and little to no medical benefit." In contrast, CBD is legal when derived from hemp, which is the same species of plant as cannabis and contains less than 0.3% THC.

To fully understand the potential impact of marijuana, it's important to know that the human body naturally produces compounds called endocannabinoids that are similar to those in marijuana. Endocannabinoids are involved in the regulation of many body processes throughout life (including learning, memory, pain control and sleep), and the action of endocannabinoids is essential to prenatal brain development and to brain maturation during adolescence.

Endocannabinoids, as well as THC, can attach to neurons in the brain through molecules called cannabinoid receptors. When THC activates cannabinoid receptors in the brain, it can disrupt the normal actions of endocannabinoids. "These receptors are highly concentrated in brain areas related to cognition," said Testai.

According to the statement, previous animal studies (in rodents) indicate that prolonged exposure to THC disrupts memory and learning, and impacts brain development and maturation in specific ways if exposed at certain stages of life:

• During prenatal life, an important time for brain development, THC disrupts the normal signaling pathways of the endocannabinoid system and may alter the offspring's thinking, emotional behavior and response to stress.

• During adolescence, an important time for brain maturation, THC changes the structure and function of brain circuits, particularly in areas involved in cognition, emotional regulation and social behavior (such as the prefrontal cortex and hippocampus).

"Data obtained in these animal studies demonstrate that disruption of endocannabinoid pathways leads to behavioral and cognitive abnormalities, such as poorer memory and learning ability and a heightened sensitivity to stress. Also, there may be vital life periods -- gestation and adolescence -- when the brain may be particularly vulnerable to the impact of THC," Testai said.

While the exact timing and amount of marijuana exposure are more easily controlled in animal studies, as well as controlling the animals' social and environmental conditions, human research studies cannot replicate similar strict parameters. Thus, results from existing studies in humans have been mixed, yet raise similar concerns about the impact of marijuana exposure on brain health. Among the studies in humans summarized in the scientific statement, the findings included:

• While actively using marijuana, people demonstrated worse scores on driving road tests when using THC-dominant marijuana, compared to when they were using CBD-dominant marijuana or no marijuana.

• In young adults who were followed for 25 years as part of a heart disease research project, scores on verbal memory tests declined in correlation to more years of self-reported exposure to marijuana.

• There were more psychological problems and poorer cognitive function in children (average age 9) whose mothers reported using marijuana during pregnancy.

• Marijuana use during adolescence has been associated with thinning in an area of the brain involved in cognition (the prefrontal cortex), with greater exposure to marijuana associated with more thinning. However, other studies detected no difference.

• Structural changes in the brain were visible in some studies comparing marijuana users and non-users. Specifically, there was thinning of brain areas important in orchestrating thoughts and actions, or decreased volume in an area of the brain important for memory. Other studies that compared cognitive testing and brain imaging found no differences between marijuana users and non-users.

• Cannabis users were found to have an increased risk of clot-caused stroke, with one study finding 17% more and another finding 24% more strokes among cannabis users.

The statement also highlights numerous open questions on the impact of cannabis on brain health, including:

• Does marijuana's impact on brain health differ depending on the person's age?

• How does marijuana interact with other substances such as prescription medications? This is a particular concern in elderly people who may be using multiple medications such as blood thinners, antiarrhythmia or anticonvulsant medications to treat other chronic health conditions.

• Do the effects of marijuana differ whether it is used recreationally or prescribed for the treatment of a specific medical condition?

• How much marijuana is too much? In older research studies conducted when marijuana was illegal in all U.S. states, there may have been significant under-reporting of how frequently marijuana was used.

• Do different types of marijuana (such as higher THC levels or synthetic cannabinoids) impact the brain differently?

• Are there differences in brain health depending on whether marijuana is smoked or consumed in an edible product?

"Our understanding of the effects of marijuana on the brain is imperfect, and human research in this area is a work in progress. Still, the results of recent animal studies challenge the widely accepted idea that cannabinoids are harmless and call for caution when using marijuana, particularly while pregnant or during adolescence," said Testai.

This scientific statement was prepared by the volunteer writing group on behalf of the American Heart Association's Stroke Brain Health Science Subcommittee of the Stroke Council; the Council on Arteriosclerosis, Thrombosis and Vascular Biology; the Council on Cardiovascular and Stroke Nursing; the Council on Lifestyle and Cardiometabolic Health; and the Council on Peripheral Vascular Disease. The American Academy of Neurology has affirmed this scientific statement as an educational tool for neurologists.

American Heart Association scientific statements promote greater awareness about cardiovascular diseases and stroke issues and help facilitate informed health care decisions. Scientific statements outline what is currently known about a topic and what areas need additional research. While scientific statements inform the development of guidelines, they do not make treatment recommendations. American Heart Association guidelines provide the Association's official clinical practice recommendations.

https://www.sciencedaily.com/releases/2022/02/220210084937.htm

Can You Retrain the Brain After Addiction?

Guest post by Dr. Harshi Dhingra
Pathologist, Assistant professor, Pathology | Adesh institute of medical sciences and research, Bathinda

Addiction is not just a physical problem but an emotional challenge that can seriously impact your life and development. It literally reprograms your brain and makes it feel nearly impossible to overcome. Thankfully, that doesn't have to be the case if you understand how to retrain your brain.

How Addiction Affects the Brain

Substance abuse will inevitably change the way that your brain operates. That's because it changes the chemistry in your mind and causes changes in how it works. This process is a multi-faceted one and impacts even people who try a few drugs:

• The Production of the High – When you get high, your brain is forced to release artificially high levels of dopamine. This release can acclimate your brain to this higher level and make life without drugs seem duller or less happy. But, unfortunately, your brain may also release fewer endorphin chemicals without drugs.

• A Decrease in Potency – You probably noticed that you get less of a higher and a shorter one the longer you use drugs. That's because your brain is retrained to tolerate higher doses, meaning you have to increase your levels (and increase your addiction) to get the same types of effects.

• The Rewarding of Adverse Patterns of Behavior – As you abuse drugs and experience higher highs, your brain becomes reprogrammed. It starts recognizing negative patterns of behavior as rewarding. As a result, it unconsciously triggers more elevated rates of substance abuse.

• A Loss of Self-Control – People who abuse substances often claim that they can’t control their actions. This perception is accurate to an extent. While they are still accountable for their behaviors, their brain pushes them harder towards frequent drug abuse.

This type of reprogramming can be hard to fight. Some people argue that addiction trains the brain in such a way that retraining is impossible. But is that the case? Let's take a look at two different arguments to get an idea of what is possible in this situation.

Brains Can't Be Retrained?

Brain plasticity is the measurement of how easy it is for your mind to adapt to new situations. Plasticity is at its peak when you're about 5-8 years old and rapidly decreases as you age. By the time you reach your 20s, it’s nowhere near what it was when you were a teen. Unfortunately, this may make retraining very difficult.

Some even argue that retraining at this point is impossible, particularly when your brain is affected by addiction. The unconscious mind has been crafted to suit specific situations and react in particular ways. As a result, adaptation can feel nearly impossible for many people, making addiction tough to fight.

That said, it is unfair to say that the brain cannot be retrained at all. Even older adults learn hobbies like painting, music, and much more. And while addiction is more complex than learning how to play guitar, you can still retrain your brain if you take the time and energy to learn how to do it.

Brains CAN Be Retrained

While retraining your brain after addiction is challenging due to decreased brain plasticity, you can retrain yourself given enough time. These steps require you to pay close attention to your behaviors and your thoughts and to condition yourself to avoid them. A few ways you can take this approach include:

• Work Towards Personal Awareness – Pay attention to your thoughts as they happen and try to understand where they originate. If they are negative, correct them with positive statements. Your brain plasticity may slow down your retraining, but consistency minimizes any confusion.

• Understand Your Triggers – Your drug addiction operates on a pattern that is unique to you. Your triggers initiate this pattern. Learning to avoid your triggers can retrain your brain. For example, if boredom pushes you towards regular drug abuse, find a way to keep yourself engaged.

• Stay Consistent – The most challenging part about retraining your brain is staying consistent. It is only through repeated and constant retraining that you can improve your mental health and fight drug addiction. You may also need a specialist or friend who can keep you engaged with this process.

• Know What You Want – The brain needs direction during retraining and an understanding of what you want. Fighting for your sobriety gives you the kind of insight that you need to stay focused and happy within your recovery effort.

These steps seem simple on the surface but can be challenging to execute correctly. You may find yourself falling away from these steps or even relapsing. Even a relapse, however, can be a powerful learning tool for retraining. Use every resource available to keep your drug addiction at bay.

Help is Available for You

Retraining your brain after addiction isn’t going to be easy. You need to work constantly at keeping yourself engaged with your growth and must recognize and actively fight negative thoughts. The mind is a very stubborn and tricky beast to battle as we age. Thankfully, it’s still possible to get help if you fully understand the different suggestions for your needs.

Just as importantly, you need to take the time to work with professionals who fully understand your needs and your emotional situation. These experts will guide you through this period, teaching you various coping mechanisms, recognizing signs of relapse, and ensure that you stay focused on the path towards recovery. While challenging, you can retrain your brain and stay sober for good.

Sources:

addiction.surgeongeneral.gov – The Neurobiology of Substance Use, Misuse, and Addiction

teens.drugabuse.gov – Brain and Addiction

ncbi.nlm.nih.gov – The Aging Mind: Neuroplasticity in Response to Cognitive Training

ncbi.nlm.nih.gov – The Social Brain: Neural Basis of Social Knowledge

ncbi.nlm.nih.gov – Brain Plasticity and Behavior in the Developing Brain

pubmed.ncbi.nih.gov – Retraining the Addicted Brain

newsinhealth.nih.gov – Biology of Addiction

drugabuse.gov – How Science Has Revolutionized the Understanding of Drug Addiction

sunshinebehavioralhealth.com - 90 Day Rehab Programs

Cannabis terpenes provide pain relief, contribute to 'entourage effect'

July 14, 2021

Science Daily/University of Arizona Health Sciences

When it comes to the medicinal and therapeutic properties of Cannabis sativa, an unsolved mystery is whether there exists an "entourage effect," whereby the pain-relieving effects of the plant as a whole are greater than any of its individual parts. New research from the University of Arizona Health Sciences has found evidence that favors the entourage effect theory and positions Cannabis terpenes, the part of the plant that provides flavor and aroma, as a promising new target for pain therapies that would require lower doses and produce fewer side effects.

"A lot of people are taking cannabis and cannabinoids for pain," said lead researcher John Streicher, PhD, a member of the UArizona Health Sciences Comprehensive Pain and Addiction Center and associate professor of pharmacology at the College of Medicine -- Tucson. "We're interested in the concept of the entourage effect, with the idea being that maybe we can boost the modest pain-relieving efficacy of THC and not boost the psychoactive side effects, so you could have a better therapeutic."

Terpenes are aromatic compounds found in many plants and are the basic component in essential oils. The terpene linalool, for example, gives lavender its distinctive floral scent. In addition to terpenes, Cannabis sativa contains naturally occurring compounds known as cannabinoids, the most well-known of which are cannabidiol, or CBD, and tetrahydrocannabinol, or THC, the psychoactive component of cannabis.

Researchers found that Cannabis terpenes, when used by themselves, mimic the effects of cannabinoids, including a reduction in pain sensation. When combined with cannabinoids, the pain-relieving effects were amplified without an increase in negative side effects. The paper, "Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity," was published in Scientific Reports.

"It was unexpected, in a way," said Dr. Streicher. "It was our initial hypothesis, but we didn't necessarily expect terpenes, these simple compounds that are found in multiple plants, to produce cannabinoid-like effects."

Dr. Streicher and the research team, including former graduate student and first author Justin LaVigne, PhD, former undergraduate researcher Ryan Hecksel and former postdoctoral fellow Attila Kerestztes, PhD, focused on four Cannabis terpenes: alpha-humulene, geraniol, linalool and beta-pinene. They evaluated each terpene alone and in combination with WIN55,212-2, a synthetic cannabinoid agonist that stimulates the body's natural cannabinoid receptors.

When a cannabinoid such as THC enters the body, it binds to one of two cannabinoid receptors -- CB1R, which is the most abundant, or CB2R. The receptor then activates neurons that affect physiological processes and behavior. In laboratory experiments, researchers found that all four terpenes activated the CB1R, just like THC.

Behavioral studies in mouse models revealed that when administered individually, all four terpenes lowered pain sensitivity, and at least three of the four classic cannabinoid side effects: reduced pain sensation, lowered body temperature, reduced movement and catalepsy, a freezing behavior related to the psychoactive effects of cannabinoids. When terpenes were combined with WIN55,212-2, researchers saw a greater reduction in pain sensation compared with either the terpene or WIN55,212-2 alone, demonstrating a terpene/cannabinoid interaction in controlling pain.

Dr. Streicher's ongoing research is focusing on the use of terpenes in combination with opioids and for specific types of cancer-related pain. His long-term goal is to develop a dose-reduction strategy that uses terpenes -- generally recognized as safe by the U.S. Food and Drug Administration -- in combination with cannabinoids or opioids to achieve the same levels of pain relief with lower doses of drugs and fewer side effects.

https://www.sciencedaily.com/releases/2021/07/210714110455.htm

Novel study of high-potency cannabis shows some memory effects

July 8, 2021

Science Daily/Washington State University

Researchers observed participants over Zoom as they used high-potency cannabis they purchased themselves from dispensaries in Washington state, where recreational cannabis is legal. After administering cognitive tests, researchers found no impact on users' performance on decision-making tests in comparison to a sober group but did find memory impairments related to free recall, source memory and false memories. This study is one of the few to investigate cannabis flower and concentrates containing more than 10% THC

Even before the pandemic made Zoom ubiquitous, Washington State University researchers were using the video conferencing app to research a type of cannabis that is understudied: the kind people actually use.

For the study, published in Scientific Reports, researchers observed cannabis users over Zoom as they smoked high-potency cannabis flower or vaped concentrates they purchased themselves from cannabis dispensaries in Washington state, where recreational cannabis use is legal. They then gave the subjects a series of cognitive tests.

The researchers found no impact on the users' performance on decision-making tests in comparison to a sober control group but did find some memory impairments related to free recall, source memory and false memories.

While the findings are in line with previous research on low-potency cannabis, this study is one of the few to investigate cannabis that contains much more than 10% tetrahydrocannabinol (THC), the plant's main psychoactive ingredient. This is only the second known study to examine the effect of cannabis concentrates.

"Because of federal restrictions to researchers, it was just not possible to study the acute effects of these high-potency products," said Carrie Cuttler, WSU psychologist and lead researcher on the study. "The general population in states where cannabis is legal has very easy access to a wide array of high- potency cannabis products, including extremely high-potency cannabis concentrates which can exceed 90% THC, and we've been limited to studying the whole plant with under 10% THC."

While 19 states and Washington D.C. have legalized cannabis for recreational use, the U.S. federal government still classifies it as a Schedule 1 drug, implying it has a high potential for abuse and no medicinal benefits. Until recently, researchers interested in studying cannabis were limited to using low-potency plants of around 6% THC supplied by the National Institute of Drug Abuse. In June, the U.S. Drug Enforcement Administration indicated it may allow some companies to start growing cannabis for research purposes.

For this study, which began in 2018, Cuttler and her colleagues found a way to study the effects of high-potency cannabis while still complying with federal guidelines. The study participants bought their own products and used them in their own homes. They were never in a laboratory on federal property, and the researchers never handled the cannabis themselves. Participants were not reimbursed for their purchase. Instead they were compensated for their time with Amazon gift cards. All participants were over 21 and experienced cannabis users who reported no past negative reactions to cannabis like panic attacks. The study's method was cleared by WSU Division of the Office of the Attorney General and the university's research ethics board.

The 80 participants were divided into four groups: two groups used cannabis flower with more than 20% THC but one containing cannabidiol (CBD), a non-psychoactive component of cannabis, and the other without CBD. Another group vaped cannabis concentrates with more than 60% THC that included CBD. A fourth group remained sober.

For all cannabis using groups, the researchers found no effect on a range of decision-making tests including risk perception and confidence in knowledge. On a few memory tests there were also no significant differences between the cannabis-using and sober groups, including prospective memory, the ability to remember to do things at a later time, such as attend an appointment. The cannabis-using participants also did well on temporal order memory, the ability to remember the sequence of previous events.

However, the groups that smoked cannabis flower with CBD did worse on verbal free recall trials- they were unable to recall as many words or pictures that were shown to them compared to the sober group. This finding was contrary to a small number of previous studies indicating CBD might have a protective effect on memory. The groups that used cannabis without CBD and the group that used concentrates, performed worse on a measure of source memory which means being able to distinguish the way previously learned information was presented.

Finally, all three cannabis-using groups did poorly on a false memory test -- when given a new word and asked if it had been presented before, they were more likely to say it had when it had not.

There was also an unexpected finding: people who vaped the high-potency concentrates with more than 60% THC performed comparably to those who smoked cannabis flower. This may have been because they tended to self-titrate -- using less of the drug to achieve a similar level of intoxication and impairment as the people who smoked the less-potent cannabis flower.

Cuttler said this was cause for cautious optimism on the little-studied but widely available concentrates.

"There's been a lot of speculation that these really high-potency cannabis concentrates might magnify detrimental consequences, but there's been almost zero research on cannabis concentrates which are freely available for people to use," said Cuttler. "I want to see way more research before we come to any general conclusion, but it is encouraging to see that the concentrates didn't increase harms."

https://www.sciencedaily.com/releases/2021/07/210708083849.htm

Psychedelic spurs growth of neural connections lost in depression

July 5, 2021

Science Daily/Yale University

The psychedelic drug psilocybin, a naturally occurring compound found in some mushrooms, has been studied as a potential treatment for depression for years. But exactly how it works in the brain and how long beneficial results might last is still unclear.

In a new study, Yale researchers show that a single dose of psilocybin given to mice prompted an immediate and long-lasting increase in connections between neurons. The findings are published July 5 in the journal Neuron.

"We not only saw a 10% increase in the number of neuronal connections, but also they were on average about 10% larger, so the connections were stronger as well," said Yale's Alex Kwan, associate professor of psychiatry and of neuroscience and senior author of the paper.

Previous laboratory experiments had shown promise that psilocybin, as well as the anesthetic ketamine, can decrease depression. The new Yale research found that these compounds increase the density of dendritic spines, small protrusions found on nerve cells which aid in the transmission of information between neurons. Chronic stress and depression are known to reduce the number of these neuronal connections.

Using a laser-scanning microscope, Kwan and first author Ling-Xiao Shao, a postdoctoral associate in the Yale School of Medicine, imaged dendritic spines in high resolution and tracked them for multiple days in living mice. They found increases in the number of dendritic spines and in their size within 24 hours of administration of psilocybin. These changes were still present a month later. Also, mice subjected to stress showed behavioral improvements and increased neurotransmitter activity after being given psilocybin.

For some people, psilocybin, an active compound in "magic mushrooms," can produce a profound mystical experience. The psychedelic was a staple of religious ceremonies among indigenous populations of the New World and is also a popular recreational drug.

It may be the novel psychological effects of psilocybin itself that spurs the growth of neuronal connections, Kwan said.

"It was a real surprise to see such enduring changes from just one dose of psilocybin," he said. "These new connections may be the structural changes the brain uses to store new experiences."

https://www.sciencedaily.com/releases/2021/07/210705113923.htm

Research shows pain relieving effects of CBD

April 25, 2021

Science Daily/Syracuse University

It's been hailed as a wonder drug and it's certainly creating wonder profits. By some estimates, the Cannabidiol (or CBD) market could be worth $20 billion dollars by 2024.

While users tout its effectiveness in pain relief, up until now there's been limited experimental human research on the actual effectiveness of the drug. However, a new study led by University researchers sheds light on the ability of CBD to reduce pain along with the impact that the so-called placebo effect may have on pain outcomes.

"For science and the public at large the question remained, is the pain relief that CBD users claim to experience due to pharmacological effects or placebo effects," says Martin De Vita, a researcher in the psychology department in the College of Arts and Sciences. "That's a fair question because we know that simply telling someone that a substance has the ability to relieve their pain can actually cause robust changes in their pain sensitivity. These are called expectancy effects."

De Vita, along with Stephen Maisto, research professor and professor emeritus of psychology, were uniquely prepared to answer that exact question. The pair, along with fellow lab member and doctoral candidate Dezarie Moskal, previously conducted the first systematic review and meta-analysis of experimental research examining the effects cannabinoid drugs on pain.

As the first experimental pain trial to examine CBD, their study yielded consistent and noteworthy results. Among other findings, the data showed that CBD and expectancies for receiving CBD do not appear to reduce experimental pain intensity, but do make the pain feel less unpleasant.

De Vita and Maisto used sophisticated equipment that safely induces experimental heat pain, allowing them to measure how the recipient's nervous system reacts and responds to it. "Then we administer a drug, like pure CBD, or a placebo and then re-assess their pain responses and see how they change based on which substance was administered," says De Vita.

Researchers then took it a step farther by manipulating the information given to participants about which substances they received. In some cases, participants were told that they got CBD when they actually received a placebo, or told they would be getting a placebo when they actually got CBD.

"That way we could parse out whether it was the drug that relieved the pain, or whether it was the expectation that they had received the drug that reduced their pain," according to De Vita. "We hypothesized that we would primarily detect expectancy-induced placebo analgesia (pain relief). What we found though after measuring several different pain outcomes is that it's actually a little bit of both. That is, we found improvements in pain measures caused by the pharmacological effects of CBD and the psychological effects of just expecting that they had gotten CBD. It was pretty remarkable and surprising."

"The data is exciting but pretty complex in that different pain measures responded differently to the drug effect, to the expectancy, or both the drug and expectancy combined -- so we're still trying to figure out what is behind the differential data with different kinds of pain measures," said Maisto. "The next step is studying the mechanisms underlying these findings and figuring out why giving instructions or CBD itself causes certain reactions to a pain stimulus."

Most people think of pain as an on and off switch, you either have it or you don't. But pain, as De Vita describes it, is a complex phenomenon with several dimensions influenced by psychological and biological factors.

For example, whereas pain intensity reflects a "sensory" dimension of pain, unpleasantness represents an "affective," or emotional, aspect of pain. "If you think of pain as the noxious noise coming from a radio the volume can represent the intensity of the pain, while the station can represent the quality," says De Vita.

Results from his previous study showed that while cannabinoid drugs weren't reducing the volume of pain, they were "changing the channel making it a little less unpleasant." According to De Vita, "It's not sunshine and rainbows pleasant, but something slightly less bothersome. We replicated that in this study and found that CBD and expectancies didn't significantly reduce the volume of the pain, but they did make it less unpleasant -- it didn't bother them as much."

As part of the study De Vita and Maisto developed advanced experimental pain measurement protocols "to pop the hood and start looking at some of these other mechanistic pain processes," says De Vita. "It's not just pain, yes or no, but there are these other dimensions of pain, and it would be interesting to see which ones are being targeted. We found that sometimes pharmacological effects of CBD brought down some of those, but the expectancies did not. Sometimes they both did it. Sometimes it was just the expectancy. And so, we were going into this thinking we were going to primarily detect the expectancy-induced pain relief but what we found out was way more complex than that and that's exciting."

One important note to also consider is the source of the CBD. "What we used in our study was pure CBD isolate oil," says De Vita. "Commercially available CBD products differ in their content and purity, so results might be different for different CBD products, depending on what other compounds they may or may not contain."

https://www.sciencedaily.com/releases/2021/04/210423130221.htm

Predicting who may do best with psychedelic-assisted therapy

Being open to new experiences associated with positive effects

March 22, 2021

Science Daily/Ohio State University

As psychedelics gain ground as a potential therapy for mental health disorders, there remains a pressing concern that patients in clinical trials may have adverse effects to the drugs.

New research identifies personality traits that have been associated with positive and negative experiences on psychedelics in previous studies, information that could help predict how future clinical trial participants will respond to the drugs.

The findings suggest that people more open to new experiences and willing to surrender to the unknown may be best positioned to have a positive experience on psychedelics, and individuals who tend to be preoccupied or apprehensive could be more likely to have a negative, or challenging, experience.

These predictions could be used by scientists to help hesitant clinical trial patients feel more open to the potential therapy, possibly by offering lower doses as a starting point, researchers say -- though such a concept remains speculative.

"The findings point to interesting testable things we can look at in future research," said Alan Davis, assistant professor of social work at The Ohio State University and senior author of the review. "It might be plausible to use threshold doses that are smaller than those used in a trial as a first exposure so people have less anxiety, experience the benefit and, from that, go into a higher dose later."

The study is published online in the journal ACS Pharmacology & Translational Science.

To arrive at these predictions, the researchers reviewed 14 published clinical trials and other types of studies conducted in recent years that documented participants' personality traits or states of mind and their associations with a positive or negative experience on psychedelics.

"It's been an open question so far in psychedelic science: How can we predict how people will react? We thought this review would be a good opportunity to develop a narrative of what the consensus is so far," said study first author Jacob Aday, a PhD candidate in psychology at Central Michigan University who collaborates with Davis.

Preliminary evidence has suggested that psychedelics may be effective in treating mood, anxiety, trauma-based and substance use disorders.

"Psychedelics might broadly apply to a whole range of different psychiatric problems, and in part that might be because they're directly affecting neurotransmission and the brain's ability to communicate in new ways that involve different parts of the brain," Davis said. "But there is still a lot to unpack about exactly how this all works and why it may be effective."

Of the studies reviewed, 10 tested psilocybin (commonly known as magic mushrooms) as a therapy, two involved LSD, one used a hallucinogenic brew called ayahuasca and one examined psychedelic use in general.

Experiences on psychedelics vary in intensity and tend to comprise three categories: a mystical, insightful or challenging experience. A mystical experience can feel like a spiritual connection to the divine, an insightful experience increases people's awareness and understanding about themselves, and a challenging experience relates to emotional and physical reactions such as anxiety or increased arousal.

The review suggests that people who are high in the traits of openness, acceptance and absorption -- the tendency to immerse oneself into imaginative experiences -- and in a psychological state of surrendering to whatever may transpire are more likely to have positive psychedelic experiences.

A state of surrender, in particular, stood out for its association with a lower chance for acute dread and a higher likelihood of a mystical experience and what is known as "ego dissolution," when one's sense of self gives way to a closer connection to other people and the broader world.

In contrast, people who are low in those traits or who are in preoccupied, apprehensive or confused states are considered more likely to experience adverse reactions.

"There was also tentative evidence that increased experience with psychedelics and increased age were associated with slightly less intense effects with the drugs," Aday said. "And there weren't any differences according to sex. Men and women responded similarly."

Three studies had identified potential neurological markers that could help predict research participant reactions to psychedelics, but the cost of collecting brain scans to screen trial candidates made them less practical predictors than psychological traits, Aday said.

Davis has already considered potential reactions to psychedelics for a psilocybin trial he is planning for veterans who have post-traumatic stress disorder.

"People who have experienced trauma are not very high in surrender, because they are anxious all the time about their past traumatic experiences," he said. "A possibility to explore is starting with a low or moderate dose prior to giving the full therapeutic dose, which might help them increase in surrender. We've designed the study this way, thinking that might be helpful."

https://www.sciencedaily.com/releases/2021/03/210322121311.htm

Medical cannabis can reduce essential tremor: Turns on overlooked cells in central nervous system

March 19, 2021

Science Daily/University of Copenhagen - The Faculty of Health and Medical Sciences

Medical cannabis is a subject of much debate. There is still a lot we do not know about cannabis, but researchers from the Department of Neuroscience at the Faculty of Health and Medical Sciences have made a new discovery that may prove vital to future research into and treatment with medical cannabis.

Cannabinoids are compounds found in cannabis and in the central nervous system. Using a mouse model, the researchers have demonstrated that a specific synthetic cannabinoid (cannabinoid WIN55,212-2) reduces essential tremor by activating the support cells of the spinal cord and brain, known as astrocytes. Previous research into medical cannabis has focussed on the nerve cells, the so-called neurons.

'We have focussed on the disease essential tremor. It causes involuntary shaking, which can be extremely inhibitory and seriously reduce the patient's quality of life. However, the cannabinoid might also have a beneficial effect on sclerosis and spinal cord injuries, for example, which also cause involuntary shaking', says Associate Professor Jean-François Perrier from the Department of Neuroscience, who has headed the research project.

'We discovered that an injection with the cannabinoid WIN55,212-2 into the spinal cord turns on the astrocytes in the spinal cord and prompts them to release the substance adenosine, which subsequently reduces nerve activity and thus the undesired shaking'.

Targeted treatment with no problematic side effects

That astrocytes are part of the explanation for the effect of cannabis is a completely new approach to understanding the medical effect of cannabis, and it may help improve the treatment of patients suffering from involuntary shaking.

The spinal cord is responsible for most our movements. Both voluntary and spontaneous movements are triggered when the spinal cord's motor neurons are activated. The motor neurons connect the spinal cord with the muscles, and each time a motor neuron sends impulses to the muscles, it leads to contraction and thus movement. Involuntary shaking occurs when the motor neurons send out conflicting signals at the same time. And that is why the researchers have focussed on the spinal cord.

'One might imagine a new approach to medical cannabis for shaking, where you -- during the development of cannabis-based medicinal products -- target the treatment either at the spinal cord or the astrocytes -- or, at best, the astrocytes of the spinal cord', says Postdoc Eva Carlsen, who did most of the tests during her PhD and postdoc projects.

'Using this approach will avoid affecting the neurons in the brain responsible for our memory and cognitive abilities, and we would be able to offer patients suffering from involuntary shaking effective treatment without exposing them to any of the most problematic side effects of medical cannabis'.

The next step is to do clinical tests on patients suffering from essential tremor to determine whether the new approach has the same effect on humans.

https://www.sciencedaily.com/releases/2021/03/210319125519.htm

Psychedelic science holds promise for mainstream medicine

March 10, 2021

Science Daily/University of Nevada, Las Vegas

Psychedelic healing may sound like a fad from the Woodstock era, but it's a field of study that's gaining traction in the medical community as an effective treatment option for a growing number of mental health conditions.

While the study of psychedelics as medicine is inching toward the mainstream, it still remains somewhat controversial. Psychedelics have struggled to shake a "counterculture" perception that was born in the 1960s, a view that had stymied scientific study of them for more than 50 years.

But that perception is slowly changing.

Mounting research suggests that controlled treatment with psychedelics like psilocybin mushrooms, LSD, and MDMA -- better known as ecstasy -- may be effective options for people suffering from PTSD, anxiety disorders, and depression. The U.S. Food & Drug Administration recently granted "breakthrough therapy" status to study the medical benefits of psychedelics. And two years ago this month, the FDA approved a psychedelic drug -- esketamine -- to treat depression.

An increasing number of states and municipalities are also grappling with calls to decriminalize psychedelic drugs, a move that UNLV neuroscientist Dustin Hines says could further the recent renaissance in psychedelic science.

"The resurgence in interest in psychedelic medicine is likely related to multiple factors, including decreasing societal stigma regarding drugs like hallucinogens and cannabis, increasing awareness of the potential therapeutic compounds found naturally occurring in plants and fungi, and the growing mental health crisis our nation faces," says Hines. "Because of the intersection between the great need for innovation and wider social acceptance, researchers have started to explore psychedelics as novel treatments for depressive disorders, including work with compounds that have been used for millennia."

In the Hines lab at UNLV, husband and wife researchers Dustin and Rochelle Hines are uncovering how psychedelics affect brain activity. Their work, published recently in Nature: Scientific Reports, shows a strong connection in rodent models between brain activity and behaviors resulting from psychedelic treatment, a step forward in the quest to better understand their potential therapeutic effects.

https://www.sciencedaily.com/releases/2021/03/210310100651.htm

CBD reduces plaque, improves cognition in model of familial Alzheimer's

March 9, 2021

Science Daily/Medical College of Georgia at Augusta University

A two-week course of high doses of CBD helps restore the function of two proteins key to reducing the accumulation of beta-amyloid plaque, a hallmark of Alzheimer's disease, and improves cognition in an experimental model of early onset familial Alzheimer's, investigators report.

The proteins TREM2 and IL-33 are important to the ability of the brain's immune cells to literally consume dead cells and other debris like the beta-amyloid plaque that piles up in patients' brains, and levels of both are decreased in Alzheimer's.

The investigators report for the first time that CBD normalizes levels and function, improving cognition as it also reduces levels of the immune protein IL-6, which is associated with the high inflammation levels found in Alzheimer's, says Dr. Babak Baban, immunologist and associate dean for research in the Dental College of Georgia and the study's corresponding author.

There is a dire need for novel therapies to improve outcomes for patients with this condition, which is considered one of the fastest-growing health threats in the United States, DCG and Medical College of Georgia investigators write in the Journal of Alzheimer's Disease.

"Right now we have two classes of drugs to treat Alzheimer's," says Dr. John Morgan, neurologist and director of the Movement and Memory Disorder Programs in the MCG Department of Neurology. One class increases levels of the neurotransmitter acetylcholine, which also are decreased in Alzheimer's, and another works through the NMDA receptors involved in communication between neurons and important to memory. "But we have nothing that gets to the pathophysiology of the disease," says Morgan, a study coauthor.

The DCG and MCG investigators decided to look at CBD's ability to address some of the key brain systems that go awry in Alzheimer's.

They found CBD appears to normalize levels of IL-33, a protein whose highest expression in humans is normally in the brain, where it helps sound the alarm that there is an invader like the beta-amyloid accumulation. There is emerging evidence of its role as a regulatory protein as well, whose function of either turning up or down the immune response depends on the environment, Baban says. In Alzheimer's, that includes turning down inflammation and trying to restore balance to the immune system, he says.

That up and down expression in health and disease could make IL-33 both a good biomarker and treatment target for disease, the investigators say.

CBD also improved expression of triggering receptor expressed on myeloid cells 2, or TREM2, which is found on the cell surface where it combines with another protein to transmit signals that activate cells, including immune cells. In the brain, its expression is on the microglial cells, a special population of immune cells found only in the brain where they are key to eliminating invaders like a virus and irrevocably damaged neurons.

Low levels of TREM2 and rare variations in TREM2 are associated with Alzheimer's, and in their mouse model TREM2 and IL-33 were both low.

Both are essential to a natural, ongoing housekeeping process in the brain called phagocytosis, in which microglial cells regularly consume beta amyloid, which is regularly produced in the brain, the result of the breakdown of amyloid-beta precursor protein, which is important to the synapses, or connection points, between neurons, and which the plaque interrupts.

They found CBD treatment increased levels of IL-33 and TREM2 -- sevenfold and tenfold respectively.

CBD's impact on brain function in the mouse model of early onset Alzheimer's was assessed by methods like the ability to differentiate between a familiar item and a new one, as well as observing the rodents' movement.

People with Alzheimer's may experience movement problems like stiffness and an impaired gait, says Dr. Hesam Khodadadi, a graduate student working in Baban's lab. Mice with the disease run in an endless tight circle, behavior which stopped with CBD treatment, says Khodadadi, the study's first author.

Next steps include determining optimal doses and giving CBD earlier in the disease process. The compound was given in the late stages for the published study, and now the investigators are using it at the first signs of cognitive decline, Khodadadi says. They also are exploring delivery systems including the use of an inhaler that should help deliver the CBD more directly to the brain. For the published studies, CBD was put into the belly of the mice every other day for two weeks.

A company has developed both animal and human inhalers for the investigators who also have been exploring CBD's effect on adult respiratory distress syndrome, or ARDS, a buildup of fluid in the lungs that is a major and deadly complication of COVID-19, as well as other serious illnesses like sepsis and major trauma. The CBD doses used for the Alzheimer's study were the same the investigators successfully used to reduce the "cytokine storm" of ARDS, which can irrevocably damage the lungs.

Familial disease is an inherited version of Alzheimer's in which symptoms typically surface in the 30s and 40s and occurs in about 10-15% of patients.

CBD should be at least equally effective in the more common, nonfamilial type Alzheimer's, which likely have more targets for CBD, Baban notes. They already are looking at its potential in a model of this more common type and moving forward to establish a clinical trial.

Plaques as well as neurofibrillary tangles, a collection of the protein tau inside neurons, are the main components of Alzheimer's, Morgan says. Beta-amyloid generally appears in the brain 15-20 years or more before dementia, he says, and the appearance of tau tangles, which can occur up to 10 years afterward, correlates with the onset of dementia. There is some interplay between beta amyloid and tau that decrease the dysfunction of each, Morgan notes.

The Food and Drug Administration is scheduled to make a ruling by early June on a new drug aducanumab, which would be the first to attack and help clear beta amyloid, Morgan says.

https://www.sciencedaily.com/releases/2021/03/210309192548.htm