This is your brain on (legal) cannabis: Researchers seek answers
For those suffering depression or anxiety, using cannabis for relief may not be the long-term answer
December 16, 2016
Science Daily/Colorado State University
For those suffering depression or anxiety, using cannabis for relief may not be the long-term answer.
That's according to new research from a team at Colorado State University seeking scientific clarity on how cannabis -- particularly chronic, heavy use -- affects neurological activity, including the processing of emotions.
Researchers led by Lucy Troup, assistant professor in the Department of Psychology, have published a study in PeerJ describing their findings from an in-depth, questionnaire-based analysis of 178 college-aged, legal users of cannabis. Recreational cannabis became legal in Colorado in 2014. Since then, seven other states have enacted legalization for recreational use, while many others allow medical use.
"One thing we wanted to focus on was the significance of Colorado, the first state to legalize recreational cannabis, and its own unique population and use that occurs here," Troup said.
Through the study, which was based solely upon self-reported use of the drug, the researchers sought to draw correlations between depressive or anxious symptoms and cannabis consumption.
They found that those respondents categorized with subclinical depression, who reported using the drug to treat their depressive symptoms, scored lower on their anxiety symptoms than on their depressive symptoms - so, they were actually more depressed than they were anxious. The same was true for self-reported anxiety sufferers: they were found to be more anxious than they were depressed.
In other words, "if they were using cannabis for self-medication, it wasn't doing what they thought it was doing," explained co-author Jacob Braunwalder, a recently graduated student researcher in Troup's lab.
Study co-author Jeremy Andrzejewski led the development of the questionnaire, called R-CUE (Recreational Cannabis Use Evaluation), that took a deep dive into users' habits, including questions about whether users smoked the drug, or consumed stronger products like hash oils or edibles. The researchers are particularly motivated to study biochemical and neurological reactions from higher-tetrahydracannabinol (THC) products available in the legal market, which can be up to 80-90 percent THC.
The researchers are quick to point out that their analysis does not say that cannabis causes depression or anxiety, nor that it cures it. But it underscores the need for further study around how the brain is affected by the drug, in light of legalization, and by some accounts, more widespread use in Colorado since legalization.
For example, said Andrzejewski, "there is a common perception that cannabis relieves anxiety." Yet research has yet to support this claim fully, he said.
Graduate student and co-author Robert Torrence pointed to past research that shows that chronic use reduces naturally occurring endocannabinoids in the brain, which are known to play a role physiological processes including mood and memory.
"There is research to suggest that cannabis can help with anxiety and depression in the beginning, but it has the reverse effect later on," said Torrence, a U.S. Army veteran who is especially interested in studying cannabis' effectiveness in treating post-traumatic stress disorders.
Due to the federal government's stringent regulations around researching cannabis, which is a schedule I drug, the general public's perception of how it affects the brain is often based in "mythos," Braunwalder said. "We want to add more information to the entire body of research."
There are currently no CSU research labs that administer cannabis to study participants, as administration of the drug for research would require special licensing and security.
Moving forward, the researchers want to refine their results and concentrate on respondents' level and length of exposure to legally available high-THC products like concentrates and hash oils, around which there has been little scientific inquiry.
"It is important not to demonize cannabis, but also not to glorify it," Troup said. "What we want to do is study it, and understand what it does. That's what drives us."
https://www.sciencedaily.com/releases/2016/12/161216115555.htm
Long-term marijuana use changes brain's reward circuit
June 7, 2016
Science Daily/Center for BrainHealth
Chronic marijuana use disrupts the brain's natural reward processes, according to researchers at the Center for BrainHealth at The University of Texas at Dallas.
In a paper published in Human Brain Mapping, researchers demonstrated for the first time with functional magnetic resonance imaging that long-term marijuana users had more brain activity in the mesocorticolimbic-reward system when presented with cannabis cues than with natural reward cues.
"This study shows that marijuana disrupts the natural reward circuitry of the brain, making marijuana highly salient to those who use it heavily. In essence, these brain alterations could be a marker of transition from recreational marijuana use to problematic use," said Dr. Francesca Filbey, director of Cognitive Neuroscience Research in Addictive Disorders at the Center for BrainHealth and associate professor in the School of Behavioral and Brain Sciences.
Researchers studied 59 adult marijuana users and 70 nonusers, accounting for potential biases such as traumatic brain injury and other drug use. Study participants rated their urge to use marijuana after looking at various visual cannabis cues, such as a pipe, bong, joint or blunt, and self-selected images of preferred fruit, such as a banana, an apple, grapes or an orange.
Researchers also collected self-reports from study participants to measure problems associated with marijuana use. On average, marijuana participants had used the drug for 12 years.
When presented with marijuana cues compared to fruit, marijuana users showed enhanced response in the brain regions associated with reward, such as the orbitofrontal cortex, striatum, anterior cingulate gyrus, precuneus and the ventral tegmental area.
"We found that this disruption of the reward system correlates with the number of problems, such as family issues, individuals have because of their marijuana use," Filbey said. "Continued marijuana use despite these problems is an indicator of marijuana dependence."
The research was funded by the National Institute on Drug Abuse.
https://www.sciencedaily.com/releases/2016/06/160607151239.htm
Heavy cannabis use associated with reduced dopamine release in brain
Effect similar to other addictions
April 14, 2016
Science Daily/Columbia University Medical Center
In a recent study, researchers found evidence of a compromised dopamine system in heavy users of marijuana. Lower dopamine release was found in the striatum -- a region of the brain that is involved in working memory, impulsive behavior, and attention. Previous studies have shown that addiction to other drugs of abuse, such as cocaine and heroin, have similar effects on dopamine release, but such evidence for cannabis was missing until now.
"In light of the more widespread acceptance and use of marijuana, especially by young people, we believe it is important to look more closely at the potentially addictive effects of cannabis on key regions of the brain," said Anissa Abi-Dargham, MD, professor of psychiatry (in radiology) at Columbia University Medical Center (CUMC) and a lead author of the paper.
The study included 11 adults between the ages of 21 and 40 who were severely dependent on cannabis and 12 matched healthy controls. On average, the cannabis group started using at age 16, became dependent on cannabis by age 20, and have been dependent for the past 7 years. In the month prior to the study, nearly all users in this study smoked marijuana daily.
Using positron emission tomography (PET) to track a radiolabelled molecule that binds to dopamine receptors in the brain, the scientists measured dopamine release in the striatum and its subregions, as well as in several brain regions outside the striatum, including the thalamus, midbrain, and globus pallidus. The cannabis users in this study stayed in the hospital for a week of abstinence to ensure that the PET scans were not measuring the acute effects of the drug. Participants were scanned before and after being given oral amphetamine to elicit dopamine release. The percent change in the binding of the radiotracer was taken as an indicator of capacity for dopamine release.
Compared with the controls, the cannabis users had significantly lower dopamine release in the striatum, including subregions involved in associative and sensorimotor learning, and in the globus pallidus.
The investigators also explored the relationship between dopamine release in a key area of the striatum and cognitive performance on learning and working memory tasks. Although there was no difference between groups in task performance, in all participants lower dopamine release was associated with worse performance on both tasks.
"We don't know whether decreased dopamine was a preexisting condition or the result of heavy cannabis use," said Dr. Abi-Dargham. "But the bottom line is that long-term, heavy cannabis use may impair the dopaminergic system, which could have a variety of negative effects on learning and behavior."
Jeffrey Lieberman, MD, Chair of Psychiatry at CUMC and past president of the American Psychiatric Association, noted that "these findings add to the growing body of research demonstrating the potentially adverse effects of cannabis, particularly in youth, at the same time that government policies and laws are increasing access and use."
https://www.sciencedaily.com/releases/2016/04/160414214826.htm
Natural 'high' could avoid chronic marijuana use
December 1, 2014
Science Daily/Vanderbilt University Medical Center
Replenishing the supply of a molecule that normally activates cannabinoid receptors in the brain could relieve mood and anxiety disorders and enable some people to quit using marijuana, a Vanderbilt University study suggests.
Cannabinoid receptors are normally activated by compounds in the brain called endocannabinoids, the most abundant of which is 2-AG. They also are "turned on" by the active ingredient in marijuana.
Sachin Patel, M.D., Ph.D., and his colleagues developed a genetically modified mouse with impaired ability to produce 2-AG in the brain. The mice exhibited anxiety-like behaviors, and female mice also displayed behaviors suggestive of depression.
When an enzyme that normally breaks down 2-AG was blocked, and the supply of the endocannabinoid was restored to normal levels, these behaviors were reversed, the researchers reported on Nov. 26 in the online edition of the journal Cell Reports.
If further research confirms that some people who are anxious and depressed have low levels of 2-AG, this method of "normalizing 2-AG deficiency could represent a viable ... therapeutic strategy for the treatment of mood and anxiety disorders," they concluded.
However, this approach has not been tested in humans, they cautioned.
Relief of tension and anxiety is the most common reason cited for chronic marijuana use. Thus, restoring depleted levels of 2-AG also "could be a way to help people using marijuana," added Patel, the paper's senior author and professor of Psychiatry and of Molecular Physiology and Biophysics.
Chronic use of marijuana down-regulates cannabinoid receptors, and thus paradoxically increases anxiety. This can lead to a "vicious cycle" of increasing marijuana use that in some cases leads to addiction.
Patel and his colleagues previously have found cannabinoid receptors in the central nucleus of the amygdala of the mouse. The amygdala is a key emotional hub in the brain involved in regulating anxiety and the flight-or-fight response.
They also have found that chemically modified inhibitors of the COX-2 enzyme they developed relieve anxiety behaviors in mice by activating natural "endocannabinoids" without gastrointestinal side effects. Clinical trials of some of these potential drugs could begin in the next several years.
Cyclooxygenase (COX) enzymes produce pro-inflammatory prostaglandins and are the target of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), used to relieve pain and inflammation. It has been known for several years that COX-2 inhibition also activates endocannabinoids.
https://www.sciencedaily.com/releases/2014/12/141201113253.htm
Chronic marijuana smoking affects brain chemistry, molecular imaging shows
June 13, 2011
Science Daily/Society of Nuclear Medicine
Definitive proof of an adverse effect of chronic marijuana use revealed at SNM's 58th Annual Meeting could lead to potential drug treatments and aid other research involved in cannabinoid receptors, a neurotransmission system receiving a lot of attention. Scientists used molecular imaging to visualize changes in the brains of heavy marijuana smokers versus non-smokers and found that abuse of the drug led to a decreased number of cannabinoid CB1 receptors, which are involved in not just pleasure, appetite and pain tolerance but a host of other psychological and physiological functions of the body.
"Addictions are a major medical and socioeconomic problem," says Jussi Hirvonen, MD, PhD, lead author of the collaborative study between the National Institute of Mental Health and National Institute on Drug Abuse, Bethesda, Md. "Unfortunately, we do not fully understand the neurobiological mechanisms involved in addiction. With this study, we were able to show for the first time that people who abuse cannabis have abnormalities of the cannabinoid receptors in the brain. This information may prove critical for the development of novel treatments for cannabis abuse. Furthermore, this research shows that the decreased receptors in people who abuse cannabis return to normal when they stop smoking the drug."
According to the National Institute on Drug Abuse, marijuana is the number-one illicit drug of choice in America. The psychoactive chemical in marijuana, or cannabis, is delta-9-tetrahydrocannabinol (THC), which binds to numerous cannabinoid receptors in the brain and throughout the body when smoked or ingested, producing a distinctive high. Cannabinoid receptors in the brain influence a range of mental states and actions, including pleasure, concentration, perception of time and memory, sensory perception, and coordination of movement. There are also cannabinoid receptors throughout the body involved in a wide range of functions of the digestive, cardiovascular, respiratory and other systems of the body. Currently two subtypes of cannabinoid receptors are known, CB1 and CB2, the former being involved mostly in functions of the central nervous system and the latter more in functions of the immune system and in stem cells of the circulatory system.
For this study, researchers recruited 30 chronic daily cannabis smokers who were then monitored at a closed inpatient facility for approximately four weeks. The subjects were imaged using positron emission tomography (PET), which provides information about physiological processes in the body. Subjects were injected with a radioligand, 18F-FMPEP-d2, which is a combination of a radioactive fluorine isotope and a neurotransmitter analog that binds with CB1 brain receptors.
Results of the study show that receptor number was decreased about 20 percent in brains of cannabis smokers when compared to healthy control subjects with limited exposure to cannabis during their lifetime. These changes were found to have a correlation with the number of years subjects had smoked. Of the original 30 cannabis smokers, 14 of the subjects underwent a second PET scan after about a month of abstinence. There was a marked increase in receptor activity in those areas that had been decreased at the outset of the study, an indication that while chronic cannabis smoking causes downregulation of CB1 receptors, the damage is reversible with abstinence.
Information gleaned from this and future studies may help other research exploring the role of PET imaging of CB1 receptors -- not just for drug use, but also for a range of human diseases, including metabolic disease and cancer.
https://www.sciencedaily.com/releases/2011/06/110606131705.htm
A quarter of problematic pot users have anxiety disorders, many since childhood
Regional data also suggest some teens who abuse pot outgrow habit in adulthood
October 24, 2017
Science Daily/Duke University Medical Center
About a quarter of adults whose marijuana use is problematic in early adulthood have anxiety disorders in childhood and late adolescence, according to new data.
The findings, publishing this week in the November issue of the Journal of the American Academy of Child and Adolescent Psychiatry, also shed light on an estimated 4 percent of adults who endured childhood maltreatment and peer bullying without resorting to chronic marijuana abuse, only to develop problems with the drug between the ages of 26 and 30.
"Given that more states may be moving towards legalization of cannabis for medicinal and recreational purposes, this study raises attention about what we anticipate will be the fastest growing demographic of users -- adults," said lead author Sherika Hill, Ph.D., an adjunct faculty associate at the Duke University School of Medicine. "A lot of current interventions and policies in the U.S. are aimed at early adolescent users. We have to start thinking about how we are going to address problematic use that may arise in a growing population of older users."
The findings are based on data from 1,229 participants in the Great Smoky Mountains Study, a long-term study of residents in 11 counties near the Appalachian Mountains in western North Carolina, where Hispanics and Latinos are underrepresented and Native Americans are overrepresented compared to the rest of the U.S.
A cohort of children in the study were enrolled as young as age 9 and have now reached their 30s. From 1993 to 2015, researchers tracked data in numerous areas of interest, including mental health, education, work attainment, and use of drugs and alcohol.
The researchers defined problematic cannabis or marijuana use as daily consumption or a habit that meets diagnostic guidelines for addiction. They tracked participants' patterns of use from the college years (ages 19-21) into adulthood (ages 26-30).
They found more than three-fourths (76.3 percent) of participants didn't use or develop a problem with marijuana during this period.
The remaining quarter developed problems that researchers grouped into three profiles -- those with limited problems, persistent problems and delayed problems.
Limited users (13 percent)
· Limited problematic users had trouble with marijuana either while in school before age 16 or in their late teens and early 20s, but their habits dropped off as they aged.
· Researchers were somewhat surprised that this group reported the highest levels of family conflict and instability during childhood as compared to others in the study; these factors are often associated with more drug use.
· "When this group of children left home, they seemed to do better," Hill said. "They didn't have as many children at a young age, and they went further in their education when they were 19 to 21 compared to those with persistent and delayed profiles."
Persistent users (7 percent)
· This group had trouble with marijuana beginning as young as 9 years old and their chronic use continued into their late 20s and early 30s, the data showed.
· Large portions of this group had anxiety disorders in both childhood (27 percent) and at ages 19-21 (23 percent).
· They had the highest rates of psychiatric disorders and involvement in the criminal justice system, and most said the majority of their friends were drug users, too.
· "This suggests that a focus on mental health and well-being could go a long way to prevent the most problematic use," Hill said.
Delayed users (4 percent)
· This was a small but unique group that made it through adolescence and early adulthood without problematic marijuana use, only to become habitual users between ages 26 and 30.
· Blacks were five times as likely as whites to be delayed problematic users in the late 20s and early 30s after not having trouble with the between the ages 19-21 -- a peak time for most marijuana users.
· More than half of delayed users were both bullied by peers and mistreated by caregivers as children, yet also had lower rates of anxiety, alcohol use, and other hard drug use compared to persistent users.
· "What we don't yet understand is how childhood maltreatment didn't prompt earlier problematic use of cannabis between ages 19 and 21 -- how individuals could be resilient to that kind of adverse experience for so long," Hill said. "One theory is that they were somewhat protected by having fewer peers in late adolescence who were substance users, but this is one of the questions we will continue to seek answers for."
https://www.sciencedaily.com/releases/2017/10/171024141720.htm