Psychedelic microdosing in rats shows beneficial effects

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

Traditional Amazonian drug linked to improved sense of wellbeing

November 9, 2017

Science Daily/University of Exeter

A psychedelic drug traditionally used in South America improves people's general sense of wellbeing and may offer a treatment for alcoholism and depression, new research suggests.

Ayahuasca, a psychedelic brew often used in the Amazon region, contains dimethyltryptamine (DMT) -- an illegal class A drug in the UK.

Previous research has suggested that psychedelic drugs such as LSD and magic mushrooms can help alcoholics tackle their addiction.

Using Global Drug Survey data from more than 96,000 people worldwide, researchers from the University of Exeter and University College London found that ayahuasca users reported lower problematic alcohol use than people who took LSD or magic mushrooms.

Ayahuasca users also reported higher general wellbeing over the previous 12 months than other respondents in the survey.

"These findings lend some support to the notion that ayahuasca could be an important and powerful tool in treating depression and alcohol use disorders," said lead author Dr Will Lawn, of University College London.

"Recent research has demonstrated ayahuasca's potential as a psychiatric medicine, and our current study provides further evidence that it may be a safe and promising treatment.

"It is important to note that these data are purely observational and do not demonstrate causality.

"Moreover, ayahuasca users in this survey still had an average drinking level which would be considered hazardous. Therefore, randomised controlled trials must be carried out to fully examine ayahuasca's ability to help treat mood and addiction disorders.

"However, this study is notable because it is, to the best of our knowledge, the largest survey of ayahuasca users completed to date."

Ayahuasca -- a blend of the Psychotria Viridis bush and the stems of the Banisteriopsis Caapi vine -- is used by indigenous tribes and religious groups in the Amazon region, as well as many visitors.

The online survey, which was promoted via social media, measured wellbeing using the Personal Wellbeing Index -- a tool used by researchers around the world which asks about things such as personal relationships, connection with the community and a sense of achievement.

Of the respondents, 527 were ayahuasca users, 18,138 used LSD or magic mushrooms and 78,236 did not take psychedelic drugs.

Senior author Professor Celia Morgan, of the University of Exeter, said: "If ayahuasca is to represent an important treatment, it is critical that its short and long-term effects are investigated, and safety established.

"Several observational studies have examined the long-term effects of regular ayahuasca use in the religious context.

"In this work, long-term ayahuasca use has not been found to impact on cognitive ability, produce addiction or worsen mental health problems.

"In fact, some of these observational studies suggest that ayahuasca use is associated with less problematic alcohol and drug use, and better mental health and cognitive functioning."

However, the survey data showed a higher incidence of lifetime mental illness diagnoses within the ayahuasca users. Subsequent analyses found that these were confined to users from countries without a tradition of ayahuasca use.

The researchers said future studies should examine the relationships between ayahuasca use, mental health, wellbeing and problematic alcohol and substance use among these people.

The survey also asked people about the experiences of ayahuasca, and most users said they took the drug with a healer or a shaman.

Ayahuasca was rated as less pleasant and with less of an urge to use more of it than LSD or magic mushrooms. Its acute effects usually lasted for six hours, and were most strongly felt one hour after consumption.

The paper, published in the Nature journal Scientific Reports, is entitled: "Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: a large, international, self-selecting online survey."

https://www.sciencedaily.com/releases/2017/11/171109093134.htm