Two new studies published online today in JAMA (Journal of the American Medical Association) Psychiatry provide little support for previous claims that cannabis exposure is significantly harmful to the developing brain.
The first study, which assessed the effects of cannabis exposure on brain volume in exposed and unexposed sibling pairs, reported that any identifiable differences “were attributable to common predispositional factors, genetic or environmental in origin.” By contrast, authors found “no evidence for the causal influence of cannabis exposure” on brain morphology.
The trial is “the largest study to date examining the association between cannabis exposure (ever versus never used) and brain volumes.”
The study is one of two recent clinical trials to be published in recent months rebutting the claims of a widely publicized 2014 paper which alleged that even casual marijuana exposure may be linked to brain abnormalities, particularly in the region of the brain known as the amygdala. In January, researchers writing in The Journal of Neuroscience reported “no statistically significant differences … between daily [marijuana] users and nonusers on [brain] volume or shape in the regions of interest” after researchers controlled for participants’ use of alcohol. Similarly, today’s JAMA study “casts considerable doubt on hypotheses that cannabis use … causes reductions in amygdala volumes.”
A second study appearing today in the journal assessed whether cannabis use during adolescence is associated with brain changes that may be linked to an increased risk of schizophrenia. While researchers reported finding an association among male subjects who possessed a high genetic predisposition toward schizophrenia, authors reported that no such association existed among male subjects who were at low risk for the disease, or among females in either the high risk or low risk categories. The finding is consistent with the theory that early onset cannabis use may potentially exacerbate symptoms in a minority of subjects predisposed to the disease, but it contradicts claims that marijuana exposure is a likely cause of schizophrenia, particularly among those who are not already vulnerable to the disease.
Abstracts of both new studies appear online in JAMA Psychiatry here and here.
It was less than a year ago when the mainstream media was chock-full of headlines like this one: ‘Brain changes associated with casual marijuana use in young adults, study finds.’ The alarmist headlines were in response to a controversial paper published by researchers at Harvard University in Boston and Northwestern University in Chicago which alleged to have found differences in brain morphology in a cohort of 20 college-age marijuana users as compared to 20 non-users. The study’s investigators attributed the differences to subjects’ cannabis use.
But a funny thing happened when a team of scientists from the University of Colorado and the University of Kentucky tried to replicate these results in a separate, larger sample (158 participants) of subjects after rigorously controlling for both groups’ use of alcohol.
Writing in the January 28 edition of The Journal of Neuroscience, authors summarized:
“[T]his retrospective study examined brain morphology in a sample of adult daily marijuana users (n = 29) versus nonusers (n = 29) and a sample of adolescent daily users (n = 50) versus nonusers (n = 50). Groups were matched on a critical confounding variable, alcohol use, to a far greater degree than in previously published studies.
We acquired high-resolution MRI scans, and investigated group differences in gray matter using voxel-based morphometry, surface-based morphometry, and shape analysis in structures suggested to be associated with marijuana use, as follows: the nucleus accumbens, amygdala, hippocampus, and cerebellum.
No statistically significant differences were found between daily users and nonusers on volume or shape in the regions of interest. Effect sizes suggest that the failure to find differences was not due to a lack of statistical power, but rather was due to the lack of even a modest effect.”
Why the contradictory results? Investigators speculated that previously reported imaging studies failed to adequately control for the impact of alcohol, a substance that “unlike marijuana, … has been unequivocally associated with deleterious effects on brain morphology and cognition in both adults and adolescents.” In other words, researchers theorized that previously reported differences in the brain images of marijuana consumers as compared to non-users were likely because of subjects consumption of booze, not cannabis.
They concluded, “In sum, the results indicate that, when carefully controlling for alcohol use, gender, age, and other variables, there is no association between marijuana use and standard volumetric or shape measurements of subcortical structures. … [I]t seems unlikely that marijuana use has the same level of long-term deleterious effects on brain morphology as other drugs like alcohol. The press may not cite studies that do not find sensational effects, but these studies are still extremely important.”
An abstract of the study, “Daily Marijuana Use Is Not Associated with Brain Morphometric Measures in Adolescents or Adults,” is online here.
[excerpt] A new study identifying minor differences in the brain imaging of habitual marijuana consumers compared to non-users may be ideal for stimulating sensational headlines (e.g., “Regular pot smokers have shrunken brains, study says,” Los Angeles Times, November 10), but tells us little in regard to whether pot poses actual health risks.
Specifically, an MRI scan revealed less gray matter in the orbital frontal cortex of pot-smoking subjects compared to those who had never used the drug. Researchers also identified increased connectivity between certain regions of the brain in regular marijuana users compared with non-users.
So precisely what do these findings tell us in regard to pot use and health? Not much. Since the study design is not longitudinal, investigators cannot determine whether these differences are caused by subject’s cannabis use, whether these differences existed prior to subjects’ ever trying cannabis, or whether these differences persist when users’ cannabis consumption ceases.
Most importantly, investigators in this study failed to determine whether any of these differences are positively associated with any measurable adverse performance outcomes, such as cognitive performance or quality of life. It may be that these cannabis users are functioning in their daily lives in a manner that is indistinguishable from controls, in which case the imaging differences may hold little if any real-world significance. (In fact, one of the paper’s authors acknowledged, “[C]hronic users appear to be doing fine.”)
Full text of NORML’s response, “Media Leaping to Extremely Faulty Conclusions from Study on the Effects of Marijuana on the Brain,” appears online here.
Moderate cannabis consumption by young people is not positively associated with changes in intelligence quotient (IQ), according to data presented this week at the European College of Neuropsychopharmacology annual congress in Berlin, Germany.
Investigators at the University College of London analyzed data from 2,612 subjects who had their IQ tested at the age of eight and again at age 15. They reported no relationship between cannabis use and lower IQ at age 15 when confounding factors such as subjects’ history of alcohol use and cigarette use were taken into account.
“In particular alcohol use was found to be strongly associated with IQ decline,” the authors wrote in a press release cited by The Washington Post. “No other factors were found to be predictive of IQ change.”
Quoted in the Independent Business Times, the study’s lead author said: “Our findings suggest cannabis may not have a detrimental effect on cognition, once we account for other related factors particularly cigarette and alcohol use. This may suggest that previous research findings showing poorer cognitive performance in cannabis users may have resulted from the lifestyle, behavior and personal history typically associated with cannabis use, rather than cannabis use itself.”
The investigators acknowledged that more chronic marijuana use, defined in the study as a subject’s admission of having consumed cannabis 50 times or more by age 15, was correlated with slightly poorer exam results at the age of 16 — even after controlling for other variables. However, investigators admitted: “It’s hard to know what causes what. Do kids do badly at school because they are smoking weed, or do they smoke weed because they’re doing badly?”
Commenting on the newly presented data, the meeting’s Chair, Guy Goodwin, from the University of Oxford, told BBC News: “This is a potentially important study because it suggests that the current focus on the alleged harms of cannabis may be obscuring the fact that its use is often correlated with that of other even more freely available drugs and possibly lifestyle factors.”
In a recent review published in the New England Journal of Medicine, the NIDA Director Nora Volkow alleged that cannabis use, particularly by adolescents, is associated with brain alterations and lower IQ. However, the IQ study cited by Ms. Volkow as the basis of her claim was later questioned in a separate analysis published in the Proceedings of the National Academy of Sciences. That paper suggested that socioeconomics, not subjects’ cannabis use, was responsible for differences in IQ and that the plant’s “true effect [on intelligence quotient] could be zero.”
A previous assessment of cannabis use and its potential impact on intelligence quotient in a cohort of young people tracked since birth reported, “[M]arijuana does not have a long-term negative impact on global intelligence.”
The mainstream media launched into a reefer mad frenzy this week after researchers from Harvard University in Boston and Northwestern University in Chicago published the results of a neuroimaging study assessing the brains of a small cohort of regular marijuana smokers and non-users. The brain scans identified various differences between the two groups in three aspects of brain morphometry: gray matter density, volume, and shape. These differences triggered dozens of high-profile media outlets to lose their collective minds. Here’s a sampling:
Yet despite the sensationalist headlines, the study itself was hardly newsworthy. Decades of research pertaining to the potential residual adverse effects of cannabis on brain cognition have failed to support the notion that marijuana poses any sort of permanent brain deficits. And as I write today on Alternet.org, this study similarly failed to report any sort of real-world adverse consequences associated with cannabis use:
[excerpt] Using high–resolution MRI imaging, scientists identified specific changes in particular regions of the brain that they inferred were likely due to marijuana exposure. (Since researchers only performed a single MRI session, they could not say definitively whether these changes were, in fact, caused by cannabis or whether they existed prior to subjects’ use of the plant.) Notably, however, these changes did not appear to be associated with any overt adverse effects in subjects’ actual cognition or behavior. (Separate studies assessing youth use of legal intoxicants, such as nicotine and alcohol, have also been associated with documented changes in brain structure. Ditto for caffeine intake in preclinical models. These findings have received far less media attention.)
Both the cases (20 marijuana users) and controls (20 nonusers) in the study were recruited from local universities, undermining the notion that the alleged ‘brain damaged potheads’ were any more academically challenged than their non-using peers. Further, as summarized by HealthDay: “Psychiatric interviews revealed that the pot smokers did not meet criteria for drug dependence. For example, marijuana use did not interfere with their studies, work or other activities, and they had not needed to increase the amount they used to get the same high.”
In other words, case subjects and controls appeared to function similarly in their professional and academic endeavors.
You can read the full text of my response here.
[Update: I have a separate op/ed (“Smoke weed, turn into a pothead? Not so fast”) responding to this paper online in The Los Angeles Times here.]
Fortunately, my critique of this latest paper — and in particular the mainstream media’s sensationalist and erroneous coverage of its findings — is far from the only one. Below are links to several other excellent analyses:
Bits of DNA (blog): Does researching casual marijuana use cause brain abnormalities?