Low-dose THC can relieve stress

Cannabis smokers often report that they use the drug to relax or relieve stress, but few studies provide clinical evidence of these effects.

Now, researchers at the University of Illinois at Chicago and the University of Chicago report that low levels tetrahydrocannabinol, or THC, the main psychoactive compound in marijuana, does reduce stress, but in a highly dose-dependent manner: very low doses lessened the jitters of a public-speaking task, while slightly higher doses — enough to produce a mild “high” — actually increased anxiety.

Cannabis is a highly regulated category 1 substance, and permits to study the drug are difficult to obtain. While it is common knowledge that many people use cannabis for its stress-relieving effects, “very few published studies have looked into the effects of THC on stress, or at the effects of different levels of THC on stress,” says Emma Childs, associate professor of psychiatry in the UIC College of Medicine and corresponding author on the study, published in the journal Drug and Alcohol Dependence.

“We found that THC at low doses reduced stress, while higher doses had the opposite effect, underscoring the importance of dose when it comes to THC and its effects.”

Childs and her colleagues recruited 42 healthy volunteers 18 to 40 years old who had some experience with cannabis use but who were not daily users.

Participants were randomly divided into three groups: The low-dose group received a capsule containing 7.5 milligrams of THC; the moderate-dose group received a capsule containing 12.5 milligrams of THC; and a placebo group received a capsule containing none. Neither the participants nor the researchers knew who was in each group.

“The doses used in the study produce effects that are equivalent to only a few puffs of a cannabis cigarette,” said Childs, noting that it is difficult to compare doses of smoked cannabis to doses of ingested THC. “We didn’t want to include a much larger dose, because we wanted to avoid potential adverse effects or cardiovascular effects that can result from higher doses of THC.”

Participants attended two four-hour sessions at the University of Chicago, five days apart. At each session, they took their capsule and then relaxed for two hours to allow the THC to be absorbed into the bloodstream.

During one session, participants were asked to spend 10 minutes preparing for a mock job interview. They were then subjected to a five-minute interview with lab assistants who did not offer any feedback, verbally or through body language, although video display was visible to the participant, showing their performance. Participants were then instructed to count backwards from a five-digit number by subtracting 13, for five minutes — a task that is “very reliably stress-inducing,” Childs said.

In their second visit, participants were asked to talk to lab assistants about a favorite book or movie for five minutes and then play solitaire for another five minutes.

Before, during and after each of the two activities, participants rated their stress levels and feelings about the tasks. Blood pressure, heart rate, and cortisol, a key stress hormone, were measured at intervals.

The participants who received 7.5 milligrams of THC reported less stress after the psychosocial test than those given a placebo, and their stress levels dissipated faster after the test.

Participants who received 12.5 milligrams of THC before the two tasks reported greater negative mood before and throughout the task, and were more likely to rate the psychosocial task as “challenging” and “threatening” beforehand. Participants who received this dose also had more pauses during the mock interview compared to those in the placebo group.

There were no significant differences in participants’ blood pressure, heart rate or cortisol levels — before, during or after the doses or the tasks.

“Our findings provide some support for the common claim that cannabis is used to reduce stress and relieve tension and anxiety,” Childs said. “At the same time, our finding that participants in the higher THC group reported small but significant increases in anxiety and negative mood throughout the test supports the idea that THC can also produce the opposite effect.”

“Studies like these — examining the effects of cannabis and its pharmacological constituents under controlled conditions — are extremely important, considering the widespread use of cannabis for both medical and non-medical purposes,” she said.  “Unfortunately, significant regulatory obstacles make it extremely difficult to conduct this type of research — with the result that cannabis is now widely available for medical purposes with minimal scientific foundation.”

Joseph Lutz of UIC and Harriet de Wit of the University of Chicago are co-authors on the study, which was supported by grant DA02812 from the National Institute on Drug Abuse.

University of Illinois at Chicago

AMBROSIAC - A menu for brain responses opposing stress-induced alterations in cognition

Abstract

Diet and nutritional habits significantly impact on brain fitness, mental and cognitive health throughout life. The relative abundance of specific dietary nutrients, depending on intake, bioavailability and metabolism, affects mental health and cognitive ability via direct and indirect mechanisms that modulate neuronal function and synaptic plasticity. Optimum nutrition is a key determinant in the well-being of the healthy ageing population world-wide, as ageing is characterized by a decline in metabolism and homeostatic processes as well as age-related cognitive impairment over time, leading to functional decline and increased risk for disease. Chronic stress has been shown to negatively impact brain plasticity and cognitive performance, in particular in the ageing brain. Interestingly, the aged brain resembles the stressed brain on both behavioural and cellular levels and stress-induced cognitive alterations are likely to be more marked in the elderly. Likewise, poor nutritional habits are hypothesized to correlate with a heightened stress reactivity and susceptibility and greater cognitive decline in elderly, supporting the notion that interactions between nutritional factors and stress susceptibility represent critical determinants of cognitive performance and age-related cognitive decline.

Technical Summary

This proposal investigates how diet through stress-related mechanisms affects cognition across the lifespan using preclinical and clinical approaches. Particular focus will be on the influence of nutrition on increased susceptibility for stress-induced cognitive deficits in memory and executive functioning from adulthood to old age (aim 1) and the impact of a nutritional intervention on cognitive ability, stress vulnerability and stress perception (aim 2).
Next, the molecular mechanisms by which targeted nutritional interventions can improve stress-induced vulnerabilities in cognition will be investigated using preclinical models (aim 3). Throughout the 3 aims, the gut microbiota will be investigated as a novel critical signalling mediator between nutritional intake, stress susceptibility and maintenance of cognitive health in ageing (using samples from aims 1, 2 and 3). Elucidating the cellular and molecular mechanisms and pathways through which nutrition can promote the resistance of neurons to insults and enhance mental fitness will help us to determine how best to modulate diet composition in order to attenuate stress vulnerability, reduce susceptibility to metabolic disorders, and ultimately promote brain health during healthy ageing.

Planned Impact

In line with the vision of the JPI to strengthen Europe’s competiveness, AMBROSIAC aims to positively impact population health, society and the economy though influencing industry (food, pharma, biotechnology) via the project outcomes. AMBROSIAC will provide a platform to uncover the interactions between diet and targeted nutritional interventions with stress vulnerability and cognitive performance throughout life. The cooperation between several of the partners of the AMBROSIAC project is already existent, as collaborative efforts have already been initiated in the context of different research projects investigating the relationship between metabolic, nutritional and inflammatory processes and mental health, including the relationship between stress and cognition.

Research Council UK

Prebiotics may help to cope with stress

Recent study shows prebiotic fibers can help to protect beneficial gut bacteria and restore healthy sleep patterns after a stressful event.

What are some ways you cope with stresses in your life? Do you do yoga? Meditate? Exercise? Perhaps you should add taking prebiotics to that list.

Probiotics are well known to benefit digestive health, but prebiotics are less well understood. Prebiotics are certain types of non-digestible fibers that probiotic bacteria feed on, such as the fibers found in many plant sources like asparagus, oatmeal, and legumes. Certain bacteria also feed on non-fibers such as the protein lactoferrin, which also acts like a prebiotic and is found in breast milk.

According to a new study published in the online journal, Frontiers in Behavioral Neuroscience by Professor Monika Fleshner, PhD, and her team from the University of Colorado, Boulder, regular intake of prebiotics may promote beneficial gut bacteria and recovery of normal sleep patterns after a stressful episode.

“Acute stress can disrupt the gut microbiome,” explained Dr. Agnieszka Mika, a postdoctoral fellow and one of the authors of the study, “and we wanted to test if a diet rich in prebiotics would increase beneficial bacteria as well as protect gut microbes from stress-induced disruptions. We also wanted to look at the effects of prebiotics on the recovery of normal sleep patterns, since they tend to be disrupted after stressful events.”

In this experiment, test rats received prebiotic diets for several weeks prior to a stressful test condition and compared with control rats that did not receive the prebiotic-enriched diet. Interestingly, rats that ate prebiotics prior to the stressful event did not experience stress-induced disruption in their gut microbiota, and also recovered healthier sleep patterns sooner than controls.

Given that these experiments were done in rats, are these results relevant for humans? “The stressor the rats received was the equivalent of a single intense acute stressful episode for humans, such as a car accident or the death of a loved one,” said Dr. Robert S. Thompson, the lead author of the study. “A next set of studies will be looking exactly at that question - can prebiotics help humans to protect and restore their gut microflora and recover normal sleep patterns after a traumatic event?”

In the meantime, should we start including prebiotics in our diets to help cope with stress? “So far, no adverse effects from prebiotics have been reported,” said Dr. Mika, “and they are found widely in many plants, even present in breast milk, and are already commercially available.” Healthy gut bacteria and restful sleep could be your benefits.

Frontiers     

Meditation and yoga can ‘reverse’ DNA reactions which cause stress

Mind-body interventions (MBIs) such as meditation, yoga and Tai Chi don’t simply relax us; they can ‘reverse’ the molecular reactions in our DNA which cause ill-health and depression, according to a study by the universities of Coventry and Radboud.

The research, published mid-June in the journal Frontiers in Immunology, reviews over a decade of studies analysing how the behaviour of our genes is affected by different MBIs including mindfulness and yoga.

Experts from the universities conclude that, when examined together, the 18 studies – featuring 846 participants over 11 years – reveal a pattern in the molecular changes which happen to the body as a result of MBIs, and how those changes benefit our mental and physical health.

The researchers focus on how gene expression is affected; in other words the way that genes activate to produce proteins which influence the biological make-up of the body, the brain and the immune system.

When a person is exposed to a stressful event, their sympathetic nervous system (SNS) – the system responsible for the ‘fight-or-flight’ response – is triggered, in turn increasing production of a molecule called nuclear factor kappa B (NF-kB) which regulates how our genes are expressed.

NF-kB translates stress by activating genes to produce proteins called cytokines that cause inflammation at cellular level – a reaction that is useful as a short-lived fight-or-flight reaction, but if persistent leads to a higher risk of cancer, accelerated aging and psychiatric disorders like depression.

According to the study, however, people who practise MBIs exhibit the opposite effect – namely a decrease in production of NF-kB and cytokines, leading to a reversal of the pro-inflammatory gene expression pattern and a reduction in the risk of inflammation-related diseases and conditions.

The study’s authors say the inflammatory effect of the fight-or-flight response – which also serves to temporarily bolster the immune system – would have played an important role in mankind’s hunter-gatherer prehistory, when there was a higher risk of infection from wounds.

In today’s society, however, where stress is increasingly psychological and often longer-term, pro-inflammatory gene expression can be persistent and therefore more likely to cause psychiatric and medical problems.

Lead investigator Ivana Buric from the Brain, Belief and Behaviour Lab in Coventry University’s Centre for Psychology, Behaviour and Achievement said:

“Millions of people around the world already enjoy the health benefits of mind-body interventions like yoga or meditation, but what they perhaps don’t realise is that these benefits begin at a molecular level and can change the way our genetic code goes about its business.

These activities are leaving what we call a molecular signature in our cells, which reverses the effect that stress or anxiety would have on the body by changing how our genes are expressed. Put simply, MBIs cause the brain to steer our DNA processes along a path which improves our wellbeing.

More needs to be done to understand these effects in greater depth, for example how they compare with other healthy interventions like exercise or nutrition. But this is an important foundation to build on to help future researchers explore the benefits of increasingly popular mind-body activities.”

Coventry University