Study: Self-Made Human Cannabinoids May Be Key To Treating Stress-Related Disorders

We already know that humans have our own endocannabinoid systems, made to regulate a number of bodily functions with a number of cannabinoid receptors that interact with compounds like THC and CBD in cannabis. 

Brain activity patterns and neural circuits regulated by these cannabinoids derived in the brain were not well known, but new research has revealed our bodies may actually release their own cannabinoid molecules in specific circumstances, independent of external cannabinoid use.

According to a new mice study from Northwestern Medicine published in the journal Cell Reports, the brain’s key emotional center, the amygdala, releases its own cannabinoid molecules under stress. When released, these molecules work to decrease incoming stress alarms from the hippocampus, which controls memory and emotions in the brain.

The study results add further evidence to the assertion that the brain contains innate cannabinoid molecules, key to our body’s natural coping response to stress. Further, the study may indicate that impairments to this endogenous (the body’s own) cannabinoid signaling system in the brain could result in higher susceptibility to developing psychiatric disorders related to stress, like depression and post-traumatic stress disorder (PTSD).

Still, further research is needed to determine exactly how these mechanisms work in the human brain, said corresponding study author Dr. Sachin Patel.

The Human Body’s Self-Made Cannabinoids and Understanding Stress

“Stress exposure confers risk for the development or exacerbation of psychiatric disorders: from generalized anxiety and major depression to post-traumatic stress disorder,” authors state in the introduction. “Understanding stress-induced molecular-, cellular-, and circuit-level adaptations could provide critical insight into how stress is translated into affective pathology and may reveal novel therapeutic targets for the treatment of stress-related disorders.”

Scientists at Northwestern Medicine used a new protein sensor that can detect the presence of these cannabinoid molecules in real time at specific brain synapses, which show that specific high-frequency patterns of amygdala activity can generate the molecules. Additionally, the sensor showed that mice brains released these molecules in response to several different types of stress.

Scientists also removed the target of these cannabinoids, the cannabinoid receptor type 1, which resulted in a worsened ability to cope with stress and motivational deficits in mice. After scientists removed the receptor target of the endogenous cannabinoids at hippocampal-amygdala synapses, mice adopted more passive and immobile responses to stress. They also had a lower preference to drink sweetened sucrose water after stress exposure.

“Understanding how the brain adapts to stress at the molecular, cellular and circuit level could provide critical insight into how stress is translated into mood disorders and may reveal novel therapeutic targets for the treatment of stress-related disorders,” according to Patel and Lizzie Gilman, Professor of Psychiatry and Behavioral Sciences and a Northwestern Medicine psychiatrist. 

The endocannabinoid system is one of the leading signaling systems identified as a prominent drug-development candidate for stress-related psychiatric disorders, Patel said. This system is an active, complex cell signaling network, involving a combination of endocannabinoids, enzymes and cannabinoid receptors helping to regulate a number of biological functions — like eating, anxiety, learning, memory, reproduction, metabolism, growth and development — through an array of actions across the nervous system.

This hypothesis is crucial in determining where future research guides this continued conversation, Patel said.

“Determining whether increasing levels of endogenous cannabinoids can be used as potential therapeutics for stress-related disorders is a next logical step from this study and our previous work,” Patel said. “There are ongoing clinical trials in this area that may be able to answer this question in the near future.”

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Teen and Adult Smokers ‘No Less Likely to be Motivated’ Study Shows

New research once again destroys the lazy stoner stereotype, or the cannabis amotivational syndrome theory, instead showing both teen and adult cannabis consumers are “no less likely” to be motivated, nor are they less likely to show interest in rewards.

”Cannabis amotivational syndrome” is a hypothesis tossed around from commentators in the media for years that suggests regular cannabis use can lead to apathy, or less motivation, and anhedonia, or loss of interest in pleasure from rewards.

These supposed impacts on motivation are part of the hysteria surrounding teen use of cannabis while in developmental years. NORML Deputy Director Paul Armentano wrote for High Times about “the media’s absurd hysteria about teens and pot” adding that claims such as amotivational syndrome are often invented or grossly exaggerated.

But this new study examined both apathy and anhedonia levels, measured against controls to determine if stoners are truly less motivated—in the way they are often portrayed in the media.

The study was published August 24 in the International Journal of Neuropsychopharmacology.

A team led by scientists at University College London (UCL), the University of Cambridge, and the Institute of Psychiatry, Psychology & Neuroscience at King’s College London examined whether cannabis users show higher levels of apathy and anhedonia versus controls and whether they were less willing to exert physical effort to receive a reward.

The research was part of the CannTEEN study, which is also examining other factors involving teen cannabis use. For the study, 274 adults and teens were chosen if they had smoked or consumed weed at least weekly.

“Our results suggest that cannabis use at a frequency of three to four days per week is not associated with apathy, effort-based decision-making for reward, reward wanting, or reward liking in adults or adolescents,” the researchers concluded, however finding lower anhedonia in users, but with a “small effect size.”

Martine Skumlien, a PhD candidate in the Department of Psychiatry at the University of Cambridge, immediately noted the unfounded claims of the way cannabis is portrayed in the media.

“We were surprised to see that there was really very little difference between cannabis users and non-users when it came to lack of motivation or lack of enjoyment, even among those who used cannabis every day,” Skumlien said. “This is contrary to the stereotypical portrayal we see on TV and in movies.”

“There’s been a lot of concern that cannabis use in adolescence might lead to worse outcomes than cannabis use during adulthood,” Dr Will Lawn of the Institute of Psychiatry, Psychology and Neuroscience at King’s College London said. “But our study, one of the first to directly compare adolescents and adults who use cannabis, suggests that adolescents are no more vulnerable than adults to the harmful effects of cannabis on motivation, the experience of pleasure, or the brain’s response to reward.”

“In fact, it seems cannabis may have no link—-or at most only weak associations—with these outcomes in general. However, we need studies that look for these associations over a long period of time to confirm these findings.”

Over half of participants in the study carried out several tasks, with one assessing physical effort. Participants were given the option to perform button-presses in order to win points, which were later exchanged for chocolates or sweets. There were three difficulty levels and three reward levels, as more difficult trials required faster button pressing. For each test, the participant could choose to accept or reject the offer and points were only given if the test was accepted and completed.

A second task measured how much pleasure they received from rewards. The researchers found “no difference between users and non-users or between age groups on either the physical effort task or the real reward pleasure task, confirming evidence from other studies that found no, or very little, difference.”

Other recent studies also shred the cannabis amotivational syndrome theory.

A previous study, “Effort-related decision making and cannabis use among college students,” published January 27 in Experimental and Clinical Psychopharmacology, also disputes the cannabis-induced amotivational syndrome theory, finding no evidence to support it.

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