Cannabis Use Linked to Memory Dysfunction

Liam Davenport

May 07, 2015

Heavy cannabis users have an increased susceptibility to false memories, with reduced activity in brain regions linked to memory processing, and attention, and performance, new research shows

Jordi Riba, PhD, Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research, Barcelona, Spain, and colleagues found that even a month after abstaining, cannabis users were more likely than healthy control persons to believe they had seen a word before on a task.

Functional magnetic resonance imaging (fMRI) performed during the task revealed that there was reduced activity in the lateral and medial temporal lobe, along with other brain regions.

"Taken together, the present results indicate that long-term heavy cannabis users are at an increased risk of experiencing memory errors even when abstinent and drug-free," the investigators write.

Noting that the findings could have medical and legal implications, they add: "Though subtle, the deficits found bear similarities with alterations observed in psychiatric and neurologic conditions and also with age-related cognitive decline."

The research was published online March 31 in Molecular Psychiatry.

Hippocampus Affected

For the study, the researchers recruited 16 heavy cannabis users and two groups of matched control individuals. The cannabis users had used the drug an average of 42,000 times during a 21-year period, at a daily average of five joints since age 17 years. All users were required to abstain for at least 4 weeks before the study period, with urine samples taken to confirm abstinence.

Dr Riba told Medscape Medical News that it was important to study the participants after 4 weeks of abstinence because they were interested in the long-term effects of regular cannabis use, as opposed to the acute effects of the drug, while tetrahydrocannabinol (THC) is present in the body.

"THC is eliminated from the body very slowly, and heavy users usually test positive weeks after their last use. It was for this reason that we asked them to abstain for a month," he said.

All participants completed a modified version of the Deese-Roediger-McDermott memory paradigm while undergoing fMRI. For this, they were tasked with learning a series of words. They were then shown the original words, with some semantically related or unrelated additions, and were asked to identify the words from the original list.

There were no significant differences between control participants and cannabis users with regard to the number of correctly identified original and new words or in the time taken to identify or reject words.

However, cannabis users were significantly more likely than control participants to have false memories, evidenced either by their falsely recognizing a new word as previously encountered, at 12 ± 6 vs 8 ± 4 (P = .033), or by being less likely to reject a new word, at 27 ± 6 vs 32 ± 4 (P = .021).

The researchers found that on fMRI, cannabis users had reduced activation in areas linked to memory processing in the lateral and medial temporal lobe (MTL) and in the parietal and frontal regions linked to attention and performance monitoring. Cannabis consumption was also inversely correlated with MTL activity, suggesting an impact on the episodic aspects of memory.

Outlining the significance of false memories in cannabis users, Dr Riba explained that the false-memory task they used is demanding, involving the coordinated activation of different brain structures within a network that deal with memory processes, attention, and cognitive control.

"Our findings suggest that the detrimental effects affect the whole network in a subtle way," he said. "However, we saw that those participants who had a history of heavier use also showed the lowest degree of activation of the hippocampus."

"This brain structure, which is central to memory processes, would seem to be particularly vulnerable to cannabis use."

The findings also demonstrate that the false-memory effect persists for at least 1 month after abstaining. Does Dr Riba expect that the effect would wear off over time, or that it is a permanent change?

"We have not tested our participants beyond the month after stopping. My guess is that the change is reversible, even though this will probably be a slow process. Other studies have found reduced hippocampus volume 6 months after the last use," he said.

Do Risks Outweigh Benefits?

Commenting on the findings for Medscape Medical News, Chu Chen, PhD, from the Neuroscience Center of Excellence at Louisiana State University, in New Orleans, described the study as "very interesting" and "important."

He noted that the study is "a little different from what we have seen before," inasmuch as this is the first time that it has been shown that brain activity associated with memory processing is significantly reduced in heavy marijuana smokers while performing a task.

Moreover, "the findings indicate that the effect of marijuana lasts a pretty long period of time," he added.

Dr Chu said that although marijuana has medical uses, the findings underscore the need for patients to be careful, because heavy use may bring a number of undesirable effects.

Dr Riba was less cautious in his assessment of the risks posed by the medical use of marijuana.

"In many cases of therapeutic use, the benefits will probably outweigh the risks," he said.

"My greatest concern is the recreational users. They should know that minimizing the amounts taken and not allowing their use to become a daily habit should reduce the risk of experiencing memory problems."

Dr Chu noted that it is not possible, on the basis of the current findings, to deduce the way in which marijuana affects memory recall, but he speculated that perhaps heavy use affects neural circuits, even after stopping use.

"I think it would be interesting to know how long it will take to recover from previous cannabis use, like you recover other cognitive functions," he said. "Some have reported that its effects may last for long periods of time."

Dr Chu noted that this underlines just how much work there is still to do to unravel the effects of marijuana. He said: "As we know, marijuana has been used in humans for a couple of thousand years, and we do know there are a lot of undesirable psychoactive, neuronal, and cognitive deficits induced by marijuana or cannabis."

"But we still have a lot of unknowns, whether they have other deficits or maybe other beneficial effects. This we still need to work on," he concluded.

This work was supported by a grant from the Plan Nacional Sobre Drogas of the Spanish Government. Marta Valle is supported by the Fondo de Investigación Sanitaria through a grant from the Spanish Ministry of Health in collaboration with Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Barcelona. Frederic Sampedro is supported by an FPU grant from the Spanish government. The other authors have disclosed no relevant financial relationships.

Mol Psychiatry. Published online March 31, 2015. Full text

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