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Young adults who used marijuana only recreationally showed significant abnormalities in two key brain regions that are important in emotion and motivation, scientists report.
The study was a collaboration between Northwestern Medicine and Massachusetts General Hospital/Harvard Medical School.
This is the first study to show casual use of marijuana is related to major brain changes. It showed the degree of brain abnormalities in these regions is directly related to the number of joints a person smoked per week. The more joints a person smoked, the more abnormal the shape, volume and density of the brain regions.
“This study raises a strong challenge to the idea that casual marijuana use isn’t associated with bad consequences,” said corresponding and co-senior study author Hans Breiter, MD. He is a professor of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine and a psychiatrist at Northwestern Memorial Hospital.
“Some of these people only used marijuana to get high once or twice a week,” Breiter said. “People think a little recreational use shouldn’t cause a problem if someone is doing OK with work or school. Our data directly says this is not the case.”
The study was published April 16 in the Journal of Neuroscience.
‘Abnormally altered’ brain regions
Scientists examined the nucleus accumbens and the amygdala — key regions for emotion and motivation, and associated with addiction — in the brains of casual marijuana users and non-users. Researchers analyzed three measures: volume, shape and density of gray matter (where most cells are located in brain tissue) to obtain a comprehensive view of how each region was affected.
Both these regions in recreational pot users were abnormally altered for at least two of these structural measures. The degree of those alterations was directly related to how much marijuana the subjects used.
Of particular note, the nucleus acccumbens was abnormally large, and its alteration in size, shape and density was directly related to how many joints an individual smoked.
“One unique strength of this study is that we looked at the nucleus accumbens in three different ways to get a detailed and consistent picture of the problem,” said lead author Jodi Gilman, a researcher in the Massachusetts General Center for Addiction Medicine and an instructor in Psychology at Harvard Medical School. “It allows a more nuanced picture of the results.”
Examining the three different measures also was important because no single measure is the gold standard. Some abnormalities may be more detectable using one type of neuroimaging analysis method than another. Breiter said the three measures provide a multidimensional view when integrated together for evaluating the effects of marijuana on the brain.
“These are core, fundamental structures of the brain,” said co-senior study author Anne Blood, director of the Mood and Motor Control Laboratory at Massachusetts General and assistant professor of psychiatry at Harvard Medical School. “They form the basis for how you assess positive and negative features about things in the environment and make decisions about them.”
Through different methods of neuroimaging, scientists examined the brains of young adults, ages 18 to 25, from Boston-area colleges; 20 who smoked marijuana and 20 who didn’t. Each group had nine males and 11 females. The users underwent a psychiatric interview to confirm they were not dependent on marijuana. They did not meet criteria for abuse of any other illegal drugs during their lifetime.
The changes in brain structures indicate the marijuana users’ brains are adapting to low-level exposure to marijuana, the scientists said.
The study results fit with animal studies that show when rats are given tetrahydrocannabinol (THC) their brains rewire and form many new connections. THC is the mind-altering ingredient found in marijuana.
“It may be that we’re seeing a type of drug learning in the brain,” Gilman said. “We think when people are in the process of becoming addicted, their brains form these new connections.”
In animals, these new connections indicate the brain is adapting to the unnatural level of reward and stimulation from marijuana. These connections make other natural rewards less satisfying.
“Drugs of abuse can cause more dopamine release than natural rewards like food, sex and social interaction,” Gilman said. “In those you also get a burst of dopamine, but not as much as in many drugs of abuse. That is why drugs take on so much salience, and everything else loses its importance.”
The brain changes suggest that structural changes to the brain are an important early result of casual drug use, Breiter said.
“Further work, including longitudinal studies, is needed to determine if these findings can be linked to animal studies showing marijuana can be a gateway drug for stronger substances,” he noted.
Because the study was retrospective, researchers did not know the THC content of the marijuana, which can range from 5 to 9 percent or even higher in the currently available drug. The THC content is much higher today than the marijuana during the 1960s and 1970s, which was often about 1 to 3 percent, Gilman said.
Marijuana is the most commonly used illicit drug in the U.S. with an estimated 15.2 million users, the study reports, based on the National Survey on Drug Use and Health in 2008. The drug’s use is increasing among adolescents and young adults, partially due to society’s changing beliefs about cannabis use and its legal status.
A recent Northwestern study showed chronic use of marijuana was linked to brain abnormalities.
“With the findings of these two papers,” Breiter said, “I’ve developed a severe worry about whether we should be allowing anybody under age 30 to use pot unless they have a terminal illness and need it for pain.”
The research was supported by grants from the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke, all of the National Institutes of Health. The Office of National Drug Control Policy and Northwestern Medicine’s Warren Wright Adolescent Center also supported the research.
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Functional brain imaging reliably predicts which vegetative patients have potential to recover consciousness
A functional brain imaging technique known as positron emission tomography (PET) is a promising tool for determining which severely brain damaged individuals in vegetative states have the potential to recover consciousness, according to new research published in The Lancet.
Surprisingly, this is the first time that researchers have tested the diagnostic accuracy of functional brain imaging techniques in clinical practice.
“Our findings suggest that PET imaging can reveal cognitive processes that aren’t visible through traditional bedside tests, and could substantially complement standard behavioral assessments to identify unresponsive or ‘vegetative’ patients who have the potential for long-term recovery,” says study leader Professor Steven Laureys from the University of Liége in Belgium.*
Misdiagnoses of level of consciousness
In severely brain-damaged individuals, judging the level of consciousness has proved challenging. Traditionally, bedside clinical examinations have been used to decide whether patients are in a minimally conscious state (MCS), in which there is some evidence of awareness and response to stimuli, or are in a vegetative state (VS) also known as unresponsive wakefulness syndrome, where there is neither, and the chance of recovery is much lower. But up to 40% of patients are misdiagnosed using these examinations.
“In patients with substantial cerebral edema [swelling of the brain], prediction of outcome on the basis of standard clinical examination and structural brain imaging is probably little better than flipping a coin,” writes Jamie Sleigh from the University of Auckland, New Zealand, and Catherine Warnaby from the University of Oxford, UK.
PET vs. fMRI
The study assessed whether two new functional brain imaging techniques — PET with the imaging agent fluorodeoxyglucose (FDG) and functional MRI (fMRI) during mental imagery tasks — could distinguish between vegetative and MCS in 126 patients with severe brain injury (81 in a MCS, 41 in a VS, and four with locked-in syndrome — a behaviorally unresponsive but conscious control group) referred to the University Hospital of Liége, in Belgium, from across Europe.
The researchers then compared their results with the well-established standardized Coma Recovery Scale–Revised (CSR-R) behavioural test, considered the most validated and sensitive method for discriminating very low awareness.
Overall, FDG-PET was better than fMRI in distinguishing conscious from unconscious patients. (Mental imagery fMRI was less sensitive at diagnosis of a MCS than FDG-PET (45% vs 93%), and had less agreement with behavioral CRS-R scores than FDG-PET (63% vs 85%). FDG-PET was about 74% accurate in predicting the extent of recovery within the next year, compared with 56% for fMRI.)
Importantly, a third of the 36 patients diagnosed as behaviorally unresponsive on the CSR-R test who were scanned with FDG-PET showed brain activity consistent with the presence of some consciousness. Nine patients in this group subsequently recovered a reasonable level of consciousness.
According to Professor Laureys, “We confirm that a small but substantial proportion of behaviorally unresponsive patients retain brain activity compatible with awareness. Repeated testing with the CRS–R complemented with a cerebral FDG-PET examination provides a simple and reliable diagnostic tool with high sensitivity towards unresponsive but aware patients. fMRI during mental tasks might complement the assessment with information about preserved cognitive capability, but should not be the main or sole diagnostic imaging method.”
The authors point out that the study was done in a specialist unit focusing on the diagnostic neuroimaging of disorders of consciousness, so getting it used in less specialist units might be more challenging.
Commenting on the study, Sleigh and Warnaby add, “From these data, it would be hard to sustain a confident diagnosis of unresponsive wakefulness syndrome solely on behavioral grounds, without PET imaging for confirmation…[This] work serves as a signpost for future studies. Functional brain imaging is expensive and technically challenging, but it will almost certainly become cheaper and easier. In the future, we will probably look back in amazement at how we were ever able to practice without it.”
Abstract of The Lancet paper
Background – Bedside clinical examinations can have high rates of misdiagnosis of unresponsive wakefulness syndrome (vegetative state) or minimally conscious state. The diagnostic and prognostic usefulness of neuroimaging-based approaches has not been established in a clinical setting. We did a validation study of two neuroimaging-based diagnostic methods: PET imaging and functional MRI (fMRI).
Methods – For this clinical validation study, we included patients referred to the University Hospital of Liège, Belgium, between January, 2008, and June, 2012, who were diagnosed by our unit with unresponsive wakefulness syndrome, locked-in syndrome, or minimally conscious state with traumatic or non-traumatic causes. We did repeated standardised clinical assessments with the Coma Recovery Scale—Revised (CRS—R), cerebral 18F-fluorodeoxyglucose (FDG) PET, and fMRI during mental activation tasks. We calculated the diagnostic accuracy of both imaging methods with CRS—R diagnosis as reference. We assessed outcome after 12 months with the Glasgow Outcome Scale—Extended.
Findings – We included 41 patients with unresponsive wakefulness syndrome, four with locked-in syndrome, and 81 in a minimally conscious state (48=traumatic, 78=non-traumatic; 110=chronic, 16=subacute). 18F-FDG PET had high sensitivity for identification of patients in a minimally conscious state (93%, 95% CI 85—98) and high congruence (85%, 77—90) with behavioural CRS—R scores. The active fMRI method was less sensitive at diagnosis of a minimally conscious state (45%, 30—61) and had lower overall congruence with behavioural scores (63%, 51—73) than PET imaging. 18F-FDG PET correctly predicted outcome in 75 of 102 patients (74%, 64—81), and fMRI in 36 of 65 patients (56%, 43—67). 13 of 42 (32%) of the behaviourally unresponsive patients (ie, diagnosed as unresponsive with CRS—R) showed brain activity compatible with (minimal) consciousness (ie, activity associated with consciousness, but diminished compared with fully conscious individuals) on at least one neuroimaging test; 69% of these (9 of 13) patients subsequently recovered consciousness.
Interpretation – Cerebral 18F-FDG PET could be used to complement bedside examinations and predict long-term recovery of patients with unresponsive wakefulness syndrome. Active fMRI might also be useful for differential diagnosis, but seems to be less accurate.
Funding – The Belgian National Funds for Scientific Research (FNRS), Fonds Léon Fredericq, the European Commission, the James McDonnell Foundation, the Mind Science Foundation, the French Speaking Community Concerted Research Action, the University of Copenhagen, and the University of Liège.
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