Science of microdosing psychedelics remains patchy and anecdotal, say researchers

July 15, 2019

Science Daily/Imperial College London

The practice of taking small, regular doses of psychedelic drugs to enhance mood, creativity, or productivity lacks robust scientific evidence, say scientists.

The process, called microdosing, has been lauded by some, with high profile proponents in Silicon Valley. But to date, scientific evidence to support or even fully explore claims of the benefits and safety, has been lacking.

Now, an international group of researchers, led by Imperial College London and Maastricht University, has approached the issue in a wide-ranging review paper, published today in the Journal of Psychopharmacology, to tackle some of the key questions -- including what is microdosing? Is it safe? Is it legal? And are the claims of benefits from taking small amounts of psychedelics even plausible?

According to the researchers, their review aims to present evidence around several themes of microdosing psychedelics, such as LSD or psilocybin (magic mushrooms), including discussions of concerns around impacts on cardiovascular health, as well as to providing a framework for future research in the area.

"Despite so much interest in the subject, we still don't have any agreed scientific consensus on what microdosing is -- like what constitutes a 'micro' dose, how often someone would take it, and even if there may be potential health effects" said Professor David Nutt, Edmond J Safra Chair in Neuropsychopharmacology at Imperial College London and senior author of the review.

Professor Nutt and the team define microdosing as the practice of taking repeated, low doses of psychedelic substance -- at doses that do not impair a person's 'normal' functioning (a fraction of 'recreational dose') -- in order to improve well-being and enhance cognitive or emotional processes.

However, in practice, frequency may vary widely -- from a few consecutive days, to weekdays -- as may strength and potency of substances depending on what it is and where it's from.

The review explains that while most reports on microdosing to date are anecdotal and have focused on positive experiences, future research should be expanded to focus on the potential risks.

Focusing on psilocybin -- the active compound in magic mushrooms -- as one of the two most commonly used psychedelic substances (alongside LSD), and being much further along the clinical pipeline to potential approval as a treatment, the team presents the available evidence on several aspects of microdosing.

Chief among the issues raised is the lack of controlled scientific studies, the standard measure in medical science -- where the effect of a treatment is measured in those taking it against a control or placebo group (who do not take the compound). The authors also cite a lack of certainty around the doses used in previous trials, as well as where the substances came from, and their potency.

Regarding safety, they claim evidence for long-term, repeated dosing of psilocybin is lacking in humans and animals, and that there is some evidence to highlight cardiovascular risks.

Similarly, the authors describe how data on the behavioural effects of microdosing, such as increased concentration or creativity, remain patchy. Early-stage research has shown psilocybin targets specific receptors in the brain which bind to serotonin -- a chemical messenger in the brain associated with feelings of happiness, as well as learning and memory. They speculate that these changes to the activity of networks of brain cells may explain some of the reported therapeutic benefits of microdosing, such as improvement in mood, memory or productivity.

Beyond the scientific issues, the legality and regulation of substances remains a significant barrier, say the researchers. Despite the renaissance in the science of psychedelic research, the drugs in the field -- chiefly psilocybin, LSD and DMT -- remain Schedule 1 Drugs under the UN Convention and Class A under the Misuse of Drugs Act in the UK. In the UK, this currently means only researchers with a licence from the Home Office are able to obtain and test substances, and anyone obtaining substances for microdosing without a licence could face prosecution.

The team hopes that the evidence laid out in their review will go some way to focus the attention of the research community in order to answer some of the major remaining questions in the field. They write "rigorous, placebo-controlled clinical studies need to be conducted with low doses of [psilocybin] to determine whether there is any evidence for the claims of microdosers."

Dr Kim Kuypers, from Maastricht University and first author of the review, said: "This review is timely as a lot of hope is generated by positive media reports about alleged effects of microdosing. Patients might feel attracted by those reports to try it but may actually not helped by it. We try to emphasise the lack of scientific proof that microdosing is indeed effective in combatting certain symptoms and hope that this will give impetus to new lines of research in this area."

Professor Nutt added: "Researchers working in the area of psychedelics regularly receive requests from the media asking about microdosing. We hope that this critique will provide answers to all these questions in future as well as providing a framework for research."

https://www.sciencedaily.com/releases/2019/07/190715103307.htm

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

Can tiny doses of magic mushrooms unlock creativity?

Preliminary study suggests that 'microdoses' of psychedelics may enhance a person's creative problem solving abilities

October 25, 2018

Science Daily/Springer

The use of minute doses of magic mushrooms and truffles containing psychedelic substances could induce a state of unconstrained thought that may produce more new, creative ideas. "Microdosing" in this way may allow people to experience the creative benefits of psychedelic drugs without the risk of the so-called "bad trips" that often come with high doses of such substances. This is according to a new study in the Springer-branded journal Psychopharmacology which is the official journal of the European Behavioural Pharmacology Society (EBPS). The research was led by Luisa Prochazkova of Leiden University in The Netherlands and is the first study of its kind to experimentally investigate the cognitive-enhancing effects of microdosing on a person's brain function within a natural setting.

Taking a tiny fraction of a normal dose of psychedelic substances is becoming a trend in some professional circles because this is thought to stimulate brain function and enhance mental flexibility and creativity. However, experimental research that moves away from anecdotal evidence is still rare.

In this study, Prochazkova and her colleagues investigated how a microdose of a psychedelic substance affected the cognitive brain function of 36 people who were present at an event organized by the Psychedelic Society of The Netherlands. During the experimental phase, participants were set three tasks before and after they consumed on average 0.37 grams of dried truffles. The tests assessed their convergent thinking (the identification of a single solution to a problem), their fluid intelligence (the capacity to reason and solve new problems) and their divergent thinking (the ability to recognize many possible solutions). Afterwards, the researchers analyzed the active substances present in the truffles consumed by participants.

After taking the microdose of truffles, the researchers found that participants' convergent thinking abilities were improved. Participants also had more ideas about how to solve a presented task, and were more fluent, flexible and original in the possibilities they came up with. Microdosing with psychedelic substances therefore improved both the divergent and convergent thinking of participants.

These findings are in line with earlier studies that found high doses of psychedelics can enhance creative performance. The fact that participants' intelligence scores and general analytical abilities did not change suggests that the effect of the truffles is rather selective, and more to the benefit of a person's creative domain.

"Taken together, our results suggest that consuming a microdose of truffles allowed participants to create more out-of-the-box alternative solutions for a problem, thus providing preliminary support for the assumption that microdosing improves divergent thinking," explains Prochazkova. "Moreover, we also observed an improvement in convergent thinking, that is, increased performance on a task that requires the convergence on one single correct or best solution."

Prochazkova hopes that these findings will stimulate further research into the beneficial effects of microdosing psychedelics. "Apart from its benefits as a potential cognitive enhancement technique, microdosing could be further investigated for its therapeutic efficacy to help individuals who suffer from rigid thought patterns or behavior such as individuals with depression or obsessive-compulsive disorder," she explains.

https://www.sciencedaily.com/releases/2018/10/181025103329.htm