Psychedelic microdosing in rats shows beneficial effects
Crystals of N,N¬-dimethyltryptamine (DMT) imaged with polarizing microscopy. DMT is the active ingredient in the hallucinogenic drug ayahuasca. New studies from UC Davis using a rat model show that 'microdosing' or taking small doses of a psychedelic drug that do not cause hallucinations may have beneficial effects for mental health. Credit: Lindsay Cameron and Lee Dunlap
March 4, 2019
Science Daily/University of California - Davis
Microdosing -- taking tiny amounts of psychedelic drugs to boost mood and mental acuity -- is based on anecdotal reports of its benefits. Now, a study in rats suggests microdosing can provide relief for symptoms of depression and anxiety, but also has potential negative effects.
The growing popularity of microdosing -- taking tiny amounts of psychedelic drugs to boost mood and mental acuity -- is based on anecdotal reports of its benefits. Now, a study in rats by researchers at the University of California, Davis suggests microdosing can provide relief for symptoms of depression and anxiety, but also found potential negative effects. The work is published March 4 in the journal ACS Chemical Neuroscience.
"Prior to our study, essentially nothing was known about the effects of psychedelic microdosing on animal behaviors," said David Olson, assistant professor in the UC Davis departments of Chemistry and of Biochemistry and Molecular Medicine, who leads the research team. "This is the first time anyone has demonstrated in animals that psychedelic microdosing might actually have some beneficial effects, particularly for depression or anxiety. It's exciting, but the potentially adverse changes in neuronal structure and metabolism that we observe emphasize the need for additional studies."
Testing microdosing claims
Olson's group microdosed male and female rats with DMT, short for N,N-dimethyltryptamine. A psychedelic compound found in ayahuasca tea, DMT's molecular structure is embedded within the structures of popular microdosing drugs such as LSD and psilocybin. The researchers administered one-tenth of the estimated hallucinogenic dose in rats (1 milligram per kilogram of body weight) every third day for two months. Although there is no well-established definition of what constitutes a microdose, people who microdose tend to follow a similar schedule, taking one-tenth of a "trip" dose every three days. The rats were treated for two weeks before beginning behavioral tests relevant to mood, anxiety and cognitive function, and tests were completed during the two-day period between doses.
Olson's group found DMT microdosing helped rats to overcome a "fear response" in a test considered to be a model of anxiety and post-traumatic stress disorder (PTSD) in humans. The researchers also documented reduced immobility in an experiment that measures the effectiveness of antidepressant compounds. Less immobility is associated with antidepressant effects. In tests of cognitive function and sociability, the UC Davis researchers did not find any obvious impairments or improvements, which contrasts with human anecdotal reports.
Microdosing: potential risks
The team documented some potential risks: the dosing regimen significantly increased bodyweight in male rats, for example. It also caused neuronal atrophy in female rats. The latter change was unexpected, as previously Olson's group reported that rats treated with a single high dose of DMT showed increased neuronal growth. The results suggest an acute hallucinogenic dose and chronic, intermittent low doses of DMT produce very different biochemical and structural phenotypes, Olson said.
Despite the potential adverse effects of microdosing, the findings mean that it's possible to decouple the hallucinogenic effects from the therapeutic properties of these compounds.
"Our study demonstrates that psychedelics can produce beneficial behavioral effects without drastically altering perception, which is a critical step towards producing viable medicines inspired by these compounds," Olson said.
https://www.sciencedaily.com/releases/2019/03/190304100015.htm
Human minibrains reveal effects of psychedelic substance
Study brings first evidence that psychedelics interfere with molecular signaling related to learning and memory in the human brain tissue. Minibrains, also known as cerebral organoids, have been considered a breakthrough in neuroscience studies
https://www.sciencedaily.com/images/2017/10/171009084404_1_540x360.jpg
October 9, 2017
Science Daily/D'Or Institute for Research and Education
A Brazilian study, published in Scientific Reports on October 09, 2017, has identified changes in signaling pathways associated with neural plasticity, inflammation and neurodegeneration triggered by a compound from the family of dimethyltryptamine known as 5-MeO-DMT.
"For the first time we could describe psychedelic related changes in the molecular functioning of human neural tissue," states Stevens Rehen, study leader, Professor of Federal University of Rio de Janeiro (UFRJ) and Head of Research at D'Or Institute for Research and Education (IDOR).
Though recent studies have demonstrated that psychedelic substances, such as LSD (Lysergic acid diethylamide), MDMA (Methylenedioxymethamphetamine) and ayahuasca brew which contains DMT, hold therapeutic potential with possible anti-inflammatory and antidepressant effects, the lack of appropriate biological tools has been shown as a critical limitation for the identification of molecular pathways targeted by psychedelics in the brain.
In order to unveil the effects of 5-MeO-DMT, Vanja Dakic (IDOR) and Juliana Minardi Nascimento (IDOR and University of Campinas) have exposed cerebral organoids, which are 3D cultures of neural cells that mimic a developing human brain, to a single dose of the psychedelic.
By employing mass spectrometry-based proteomics to analyze cerebral organoids, they identified that 5-MeO-DMT altered the expression of nearly thousand proteins. Then, they mapped which proteins were impacted by the psychedelic substance and their role in the human brain.
Researchers found that proteins important for synaptic formation and maintenance were upregulated. Among them, proteins related to cellular mechanisms of learning and memory, key components of brain functioning.
On the other hand, proteins involved in inflammation, degeneration and brain lesion were downregulated, suggesting a potential neuroprotective role for the psychedelic substance.
"Results suggest that classic psychedelics are powerful inducers of neuroplasticity, a tool of psychobiological transformation that we know very little about," states Sidarta Ribeiro, Director of the Brain Institute of Federal University of Rio Grande do Norte (UFRN) and coauthor of the study.
According to Professor Draulio Araujo (UFRN) and coauthor of the study, ""The study suggests possible mechanisms by which these substances exert their antidepressant effects that we have been observing in our studies."
"Our study reinforces the hidden clinical potential of substances that are under legal restrictions, but which deserve attention of medical and scientific communities," Dr. Rehen said.
https://www.sciencedaily.com/releases/2017/10/171009084404.htm
Substance present in ayahuasca brew stimulates generation of human neural cells
Harmine increases the number of neural progenitors, cells that give rise to neurons, study suggests
December 7, 2016
Science Daily/D'Or Institute for Research and Education
Human neural progenitors exposed to harmine, an alkaloid presented at the psychotropic plant decoction ayahuasca, led to a 70 percent increase in proliferation of these cells. The effect of generating new human neural cells involves the inhibition of DYRK1A, a gene that is over activated in patients with Down syndrome and Alzheimer's Disease. Thus harmine could have a potential neurogenesis role and possibly a therapeutic one over cognitive deficits.
Ayahuasca is a beverage that has been used for centuries by Native South-Americans. Studies suggest that it exhibits anxiolytic and antidepressant effects in humans. One of the main substances present in the beverage is harmine, a beta-carboline which potential therapeutic effects for depression has been recently described in mice.
"It has been shown in rodents that antidepressant medication acts by inducing neurogenesis. So we decided to test if harmine, an alkaloid with the highest concentration in the psychotropic plant decoction ayahuasca, would trigger neurogenesis in human neural cells," said Vanja Dakic, PhD student and one of the authors in the study.
In order to elucidate these effects, researchers from the D'Or Institute for Research and Education (IDOR) and the Institute of Biomedical Sciences at the Federal University of Rio de Janeiro (ICB-UFRJ) exposed human neural progenitors to this beta-carboline. After four days, harmine led to a 70% increase in proliferation of human neural progenitor cells.
Researchers were also able to identify how the human neural cells respond to harmine. The described effect involves the inhibition of DYRK1A, which is located on chromosome 21 and is over activated in patients with Down syndrome and Alzheimer's Disease.
"Our results demonstrate that harmine is able to generate new human neural cells, similarly to the effects of classical antidepressant drugs, which frequently are followed by diverse side effects. Moreover, the observation that harmine inhibits DYRK1A in neural cells allows us to speculate about future studies to test its potential therapeutic role over cognitive deficits observed in Down syndrome and neurodegenerative diseases," suggests Stevens Rehen, researcher from IDOR and ICB-UFRJ.
https://www.sciencedaily.com/releases/2016/12/161207124115.htm