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Marijuana May Hurt Cognitive Function; Anti-Inflammatory Drug an Antidepressant?

Research Updates in Psychiatry

SUBSTANCE USE

Marijuana May Hurt Cognitive Function, Worse with Heavier Use

Does marijuana affect cognitive function? There seems to be no shortage of opinions on this question, but no prospective, longitudinal study has ever been published. Until now, that is. Researchers in New Zealand followed more than 1,000 subjects from their birth in 1972–1973 until age 38, to ask whether regular cannabis users showed any evidence of cognitive decline.

The answer, surprisingly (or not, depending on where you stand on the issue), was a resounding “yes.” Studying the 1,037 individuals in the famous Dunedin Study, researchers found that those who were dependent on cannabis, or even who used it regularly, experienced an overall decrease in IQ.

Moreover, the extent of decline was correlated with heavier cannabis use. Those who admitted to regular cannabis use on more than three follow-up assessments in the 38-year period, for example, lost an average of six IQ points (99.68 to 93.93) between age 13 and age 38, while those who reported it only once lost only one point. Non-users actually gained an IQ point. Decline was apparent in multiple cognitive domains, including executive function, memory, processing speed, and verbal comprehension, and again, performance was worse with heavier use.

The researchers performed multiple controls. They eliminated those with other drug or alcohol dependence, or schizophrenia, and they even controlled for years of education. With each analysis, the same trend held true, and was statistically significant. They even interviewed informants (people “who knew the subjects well”), and these independent observers noticed more attention and memory problems among subjects with heavier cannabis use. Perhaps most notably, the subset of users who were diagnosed with cannabis dependence before age 18 lost IQ points (as many as eight), while adult-onset cannabis users experienced no such decline (Meier MH et al, Proc Natl Acad Sci USA 2012, online ahead of print).

TCPR’s Take: This was an impressive study, not only for the consistency of its findings, but for its scope, involving more than 1,000 subjects followed at regular intervals over 38 years. The study may have been limited by underreporting of drug use or the lack of objective drug-use data (like urine samples), and it should not be interpreted as proof that cannabis use causes cognitive impairment.

Nonetheless, the observations that IQ loss was most concentrated in those who started using in adolescence, and the extent of loss was correlated with heavier cannabis use, argue in favor of potentially detrimental effects of cannabis on the developing brain. If you’re looking for evidence to convince your younger patients that marijuana use may predict lower IQ in adulthood, look no further.

DEPRESSION

Anti-Inflammatory Drug an Antidepressant?

It seems that not a week goes by without another research paper drawing attention to the interface between immunology and psychiatry, or about biomarkers to predict response to psychotropic medications. A recent report from researchers at Emory University weighs in on both of these issues.

Researchers recruited 60 subjects with treatment-resistant depression, some (but not all) already taking antidepressants. Half were given an infusion of the anti-inflammatory drug infliximab (Remicade) (5 mg/kg) at baseline, and then again at weeks two and six of a 12-week trial. The other half were given placebo. There was no difference between infliximab and placebo in decreasing HAM-D scores. This is not surprising, since infliximab is an antagonist of the cytokine tumor necrosis factor (TNF) with no known role in treating depression.

Some subjects did respond, though. Twenty-two subjects had elevated (>5mg/L) levels of the inflammatory biomarker hs-CRP (high-sensitivity C-reactive protein), and in this group, there was a statistically significant antidepressant response to infliximab. In subjects with high hs-CRP, the response rate was 62% (vs. 33% for placebo) and responders had a mean decrease of 3.1 points in the HAM-D. Specific symptoms that responded to infliximab included anxiety, fatigue, and suicidal ideation. Levels of hs-CRP and TNF decreased in the majority of subjects receiving infliximab, reflecting its anti-inflammatory effect.

As with any antidepressant study, some subjects who received placebo responded to the treatment, too. When the researchers looked more closely at the placebo responders, they found that these subjects had significantly lower baseline hs-CRP than non-responders (3.1 mg/L vs. 7.8 mg/L). The authors hypothesize that some “minimal level of inflammatory activity” may be necessary for an antidepressant response (even to placebo), whereas excessive inflammation may correlate with treatment resistance.

Notably, whether a subject was taking psychotropic medication (n=37) or not during the 12-week study did not influence the results (Raison CL et al, Arch Gen Psychiatry 2012; online ahead of print).

TCPR’s Take: Infliximab doesn’t cross the blood-brain barrier, so all of its effects occur in the periphery. Nevertheless, it seems to have an indirect antidepressant effect in subjects whose baseline inflammatory markers are particularly high.

Are we getting close to the day when we might order serum TNF and hs-CRP levels on our patients to predict their degree of treatment resistance or to plan an anti-inflammatory regimen first? It’s possible, although the authors point out that the small sample size and high dose of infliximab—not to mention the complexity of cytokines and inflammatory processes—makes this less likely to be used as a treatment strategy. That said, inflammation appears to have a greater role in treatment, and treatment resistance, than we may realize.

Marijuana May Hurt Cognitive Function; Anti-Inflammatory Drug an Antidepressant?

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This article was published in print 10/2012 in Volume:Issue 10:10.


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APA Reference
Spielmans,, G. (2014). Marijuana May Hurt Cognitive Function; Anti-Inflammatory Drug an Antidepressant?. Psych Central. Retrieved on December 18, 2018, from https://pro.psychcentral.com/research-updates-in-psychiatry-7/

 

Scientifically Reviewed
Last updated: 20 Jul 2014
Last reviewed: By John M. Grohol, Psy.D. on 20 Jul 2014
Published on PsychCentral.com. All rights reserved.