cannabis

Alcohol and marijuana use in adolescence linked to impaired white-matter integrity

A brain-imaging study shows adolescents who abuse alcohol and marijuana show poorer white-matter integrity, with alcohol associated with continuing damage to wiring in prefrontal regions.

Chronic use of alcohol and marijuana during youth has been associated with poorer neural and cognitive function, which appears to continue into adulthood. A new study looking specifically at white-matter changes provides more support for the idea that adolescent brains may be at particular risk from the damage that substance abuse can bring.

The brain-imaging study compared 41 adolescents (aged 16-20) with extensive marijuana- and alcohol-use histories by mid-adolescence with 51 adolescents with no such history. The study found that substance users showed poorer white matter integrity in seven tracts (right and left superior longitudinal fasciculus, right posterior thalamic radiations, right prefrontal thalamic fibers, right superior temporal gyrus white matter, right inferior longitudinal fasciculus, left posterior corona radiata).

Two brain scans were taken, at baseline and at 18 months. Substance use interviews were given every six months.

More alcohol use during the interval was associated with worse integrity in both the right and left superior longitudinal fasciculi, above and beyond baseline values in these bundles. Marijuana use didn’t predict change over time. Those who had a history of more risk-taking behaviors showed poorer integrity of the right prefrontal thalamic fibers.

The findings add to previous research showing white matter problems in youth with substance-use histories. The study points to alcohol use during adolescence being particularly problematic. It also suggests that youth who engage in risk-taking behaviors may tend to have poorly developed fronto-thalamic tracts.

All of this is particularly worrying because it is thought that maturation of the brain during adolescence is the foundation for self-control, suggesting that substance abuse during this period may have long-lasting effects on the individual’s ability to plan, organize, and self-regulate.

Reference: 

[3210] Bava, S., Jacobus J., Thayer R. E., & Tapert S. F.
(2012).  Longitudinal Changes in White Matter Integrity Among Adolescent Substance Users.
Alcoholism: Clinical and Experimental Research. n/a - n/a.

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Large drop in IQ in those who smoked marijuana regularly as teens

September, 2012

Persistent marijuana use beginning before age 18 (but not after) is associated with a significant drop in IQ in a large, long-running study.

A large long-running New Zealand study has found that people who started using cannabis in adolescence and continued to use it for years afterward showed a significant decline in IQ from age 13 to 38. This was true even in those who hadn’t smoked marijuana for some years.

The study has followed a group of 1,037 children born in 1972-73. At age 38, 96% of the 1004 living study members participated in the latest assessment. Around 5% were regularly smoking marijuana more than once a week before age 18 (cannabis use was ascertained in interviews at ages 18, 21, 26, 32, and 38 years, and this group was not more or less likely to have dropped out of the study).

This group showed an average decline in IQ of 8 points on cognitive tests at age 38 compared to scores at age 13. Such a decline was not found in those who began using cannabis after the age of 18. In comparison, those who had never used cannabis showed a slight increase in IQ. The effect was dose-dependent, with those diagnosed as cannabis dependent on three or more occasions showing the greatest decline.

While executive function and processing speed appeared to be the most seriously affected areas, impairment was seen across most cognitive domains and did not appear to be statistically significantly different across them.

The size of the effect is shown by a further measure: informants (nominated by participants as knowing them well) also reported significantly more attention and memory problems among those with persistent cannabis dependence. (Note that a decline of 8 IQ points in a group whose mean is 100 brings it down to 92.)

The researchers ruled out recent cannabis use, persistent dependence on other drugs (tobacco, alcohol, hard drugs), and schizophrenia, as alternative explanations for the effect. The effect also remained after years of education were taken into account.

The finding supports the view that the adolescent brain is vulnerable to the effects of marijuana, and that these effects are long-lasting and significant.

Some numbers for those interested: Of the 874 participants included in the analysis (those who had missed at least 3 interviews in the 25 years were excluded), 242 (28%) never used cannabis, 479 (55%) used it but were never diagnosed as cannabis-dependent, and 153 (17%) were diagnosed on at least one of the interviews as cannabis-dependent. Of these, 80 had been so diagnosed on only one occasion, 35 on two occasions, and 38 on three or more occasions. I note that the proportion of males was significantly higher in the cannabis-dependent groups (39% in never used; 49% in used but never diagnosed; 70%, 63%, 82% respectively for the cannabis-dependent).

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How marijuana impairs working memory

April, 2012

A mouse study indicates that the psychoactive component of marijuana, TCP, impairs working memory by initiating a process that ends with neural connections being weakened.

A new study explains how marijuana impairs working memory. The component THC removes AMPA receptors for the neurotransmitter glutamate in the hippocampus. This means that there are fewer receivers for the information crossing between neurons.

The research is also significant because it adds to the growing evidence for the role of astrocytes in neural transmission of information.

This is shown by the finding that genetically-engineered mice who lack type-1 cannabinoid receptors in their astroglia do not show impaired working memory when exposed to THC, while those who instead lacked the receptors in their neurons do. The activation of the cannabinoid receptor expressed by astroglia sends a signal to the neurons to begin the process that removes AMPA receptors, leading to long-term depression (a type of synaptic plasticity that weakens, rather than strengthens, neural connections).

See the Guardian and Scientific American articles for more detail on the study and the processes involved.

For more on the effects of marijuana on memory

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Cannabis disrupts synchronized brain activity

November, 2011

Effects of a cannabis-like drug on rats explain why cannabis is linked to schizophrenia and how it might impair cognition, as well as supporting our understanding of how working memory works.

Research into the effects of cannabis on cognition has produced inconsistent results. Much may depend on extent of usage, timing, and perhaps (this is speculation) genetic differences. But marijuana abuse is common among sufferers of schizophrenia and recent studies have shown that the psychoactive ingredient of marijuana can induce some symptoms of schizophrenia in healthy volunteers.

Now new research helps explain why marijuana is linked to schizophrenia, and why it might have detrimental effects on attention and memory.

In this rat study, a drug that mimics the psychoactive ingredient of marijuana (by activating the cannabinoid receptors) produced significant disruption in brain networks, with brain activity becoming uncoordinated and inaccurate.

In recent years it has become increasingly clear that synchronized brainwaves play a crucial role in information processing — especially that between the hippocampus and prefrontal cortex (see, for example, my reports last month on theta waves improving retrieval and the effect of running on theta and gamma rhythms). Interactions between the hippocampus and prefrontal cortex seem to be involved in working memory functions, and may provide the mechanism for bringing together memory and decision-making during goal-directed behaviors.

Consistent with this, during decision-making on a maze task, hippocampal theta waves and prefrontal gamma waves were impaired, and the theta synchronization between the two was disrupted. These effects correlated with impaired performance on the maze task.

These findings are consistent with earlier findings that drugs that activate the cannabinoid receptors disrupt the theta rhythm in the hippocampus and impair spatial working memory. This experiment extends that result to coordinated brainwaves beyond the hippocampus.

Similar neural activity is observed in schizophrenia patients, as well as in healthy carriers of a genetic risk variant.

The findings add to the evidence that working memory processes involve coordination between the prefrontal cortex and the hippocampus through theta rhythm synchronization. The findings are consistent with the idea that items are encoded and indexed along the phase of the theta wave into episodic representations and transferred from the hippocampus to the neocortex as a theta phase code. By disrupting that code, cannabis makes it more difficult to retain and index the information relevant to the task at hand.

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Warm weather and marijuana impair cognition in people with MS

April, 2011

A recent study found significant cognitive impairment in MS sufferers who used marijuana for relief. Another study found cognition was better in MS sufferers on cooler days.

A study involving 50 people with MS (aged 18-65), of whom half used marijuana for pain relief, has found that marijuana users performed significantly worse on tests of attention, speed of thinking, executive function and visual perception of spatial relationships between objects. Those who used marijuana were also twice as likely as non-users to be classified as globally cognitively impaired.

The two groups were matched for age, gender, level of education, IQ before diagnosis, level of disability and duration of time with MS. On average, the duration of marijuana use was 26 years, and 72% reported smoking marijuana on a daily basis while 24% reported weekly use and one person reported bi-weekly use. There were no differences between the groups on measures of depression and anxiety.

And on a less-expected note, a study involving 40 people with multiple sclerosis and 40 people without MS has found those with MS scored 70% better on cognitive tests during cooler days compared to warmer days of the year. There was no link between test scores and temperature for those without MS.

Reference: 

[2178] Honarmand, K., Tierney M. C., O'Connor P., & Feinstein A.
(2011).  Effects of cannabis on cognitive function in patients with multiple sclerosis.
Neurology. 76(13), 1153 - 1160.

The findings of the temperature study were presented at the American Academy of Neurology's 63rd Annual Meeting in Honolulu April 9 to April 16, 2011.

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Cognitive effects of heavy alcohol and marijuana use in adolescents

November, 2010

Alcohol and marijuana abuse associated with specific cognitive impairments in adolescents, but more surprisingly family history of substance abuse can also have an effect.

A study involving 48 adolescents, of whom 19 had been diagnosed with substance abuse/dependence, and 14 had a family history of substance abuse but no history of personal use, has found that greater alcohol use was associated with a significant decrease in attention and executive function (which is involved in planning and decision-making), while greater marijuana use was associated with poorer memory. Adolescents in the substance abuse group had lower scores in attention, memory, and processing speed, compared to the other groups, while those with a family history of abuse (but no personal history) had poorer visuospatial ability.

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Not all cannabis strains affect memory equally

October, 2010

Current strains of cannabis may put users at greater risk of cognitive impairment.

A study involving 134 cannabis users aged 16-23 has found that when they were smoking cannabis containing a low percentage of cannabidiol they performed much worse on the memory tests. In contrast, those smoking cannabis high in cannabidiol performed just as well on the tests when they were intoxicated as when they were sober. There were no differences in the THC content of the cannabis smoked by any of the participants (THC is the main psychoactive ingredient, which gives the characteristic ‘stoned’ feeling, and feelings of paranoia).

For the study, the participants were tested on two separate occasions — once while they were smoking their own preferred type of cannabis and were intoxicated, and once when they had not smoked for the last 24 hours and were sober.

Levels of cannabidiol in cannabis can range from virtually none to 40%. This study suggests that cannabidiol can counteract the memory-impairing effects of THC. Unfortunately, low-cannabidiol strains (like skunk) now dominate the market of street cannabis, suggesting current users will be more at risk of cognitive impairment.

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