High-Potency Cannabis Linked to Brain Damage, Experts Warn

Liam Davenport

December 15, 2015

Smoking high-potency, or "skunk"-like, cannabis may cause white matter damage in the corpus callosum, thus interfering with communication between the right and left hemispheres of the brain, experts warn.

Investigators found that users of cannabis with a high delta-9-tetrahydrocannabinol (THC) content and daily users experienced a significant increase in mean diffusivity, a measure of white matter integrity, in the corpus callosum. Notably, the changes were seen both in individuals with and without psychosis.

"There is an urgent need to educate health professionals, the public, and policy makers about the risks involved with cannabis use," lead author Silvia Rigucci, MD, Department of Neurosciences, Mental Health and Sensory Organs, Sapienza University of Rome, Italy, told Medscape Medical News.

"When assessing cannabis use, it is extremely important to gather information on how often and what type of cannabis is being used. These details can help quantify the risk of mental health problems and increase awareness on the type of damage these substances can do to the brain."

The research was published online November 27 in Psychological Medicine.

White Matter Damage

For the study, investigators recruited 56 patients with first-episode psychosis (FEP) from South East London in the United Kingdom and 43 individuals without psychosis from the same area.

Following a clinical assessment and assessment of cannabis use, the participants underwent diffusion tensor magnetic resonance imaging (DTI) of the corpus callosum, which previous studies have shown is rich in cannabinoid receptors.

The corpus callosum was virtually dissected using tractography, and the diffusion index of fractional anisotrophy, mean, axial, and radial diffusivity was calculated for each segment.

The participants were similar with respect to age, sex, ethnicity, and amount of education. Of the individuals with FEP, 70% had ever used cannabis (mean duration, 7.6 years), compared with 52% (mean duration, 7.2 years) of non-FEP individuals.

Cannabis was used daily by 70% and 50% of FEP participants and non-FEP participants, respectively; high-potency cannabis was used by 46% and 30%, respectively. The age at first use was <15 years for 32.4% of participants with FEP vs 27.3% of those without FEP.

DTI revealed that, overall, for individuals who were users of high-potency cannabis, both total mean diffusivity and total axial diffusivity in the corpus callosum were significantly higher than was the case for users of low-potency cannabis and for those who had never used the drug (P = .005 for mean diffusivity and P = .004 for axial diffusivity).

In addition, total mean diffusivity and total axial diffusivity in the corpus callosum were higher in daily cannabis users than in both occasional users and those who never used cannabis (P = .001 for mean diffusivity and P < .001 for axial diffusivity).

Prior studies have indicated that increased mean diffusivity is a marker for white matter damage and can result from changes in intra- or extracellular space. Increases in mean diffusivity may also reflect demyelination or axonal loss.

Interestingly, the white matter changes associated with use of high-potency cannabis were similar in individuals either with or without FEP. They were more pronounced in those without psychosis and were unaffected by age at first use.

These findings suggest that white matter damage in the corpus callosum is not the mechanism underpinning the apparent association between high-potency cannabis use and psychosis.

"I know that there are some arguments against a causal link between cannabis use and schizophrenia, and that there might be other confounding factors," said Dr Rigucci. "However, previous studies from our group showed that the risk of developing psychosis is greater, and onset occurs earlier, in those individuals who use more frequently and those who use cannabis with higher THC content."

Regardless, Dr Rigucci believes that the increasing availability of high-potency cannabis means that younger people in particular need to be educated about the risks associated with the drug.

"What is clear is that high-potency marijuana is more readily available than it was in the past," Dr Rigucci said. "A study earlier this year, analyzing recreational and medical marijuana, showed that the THC content in pot can reach up to almost 30%, whereas a few decades ago it was just about 10%.

"Since adolescence is the time peak initiation of cannabis use, and since previous studies have shown a relationship between the age at which regular cannabis use commenced and brain damage, there is an urgent need to develop public education to inform young people about the risks of high-potency cannabis."

"Important" Research

Approached for comment, Raul Gonzalez, PhD, associate professor of psychology, psychiatry, and immunology at the Substance Use and HIV Neuropsychology Lab, Florida International University, in Miami, described the study as "important."

He told Medscape Medical News that it "makes clear the need to take into account the strength of cannabis used by individuals, and suggests that high-potency cannabis may be more detrimental to overall brain health."

Nevertheless, the findings need to be explored in further research. Although conceding that the current study has some limitations, Dr Rigucci said that it "adds new knowledge about the potential effect of cannabis smoking on the brain that other researchers can build on."

Dr Gonzalez added: "Future studies will need to carefully take into account differences between users of high-potency vs low-potency cannabis, including the amount of alcohol and other drug use, as well as the severity of cannabis addiction.

"In this way, we can better determine if the brain differences observed are indeed due to the direct effects of cannabis as opposed to other factors."

The research was in part financially supported by a King's College London Translational Research Grant and by the National Institute for Health Research, the Mental Health Biomedical Research Centre at South London, the Maudsley NHS Foundation Trust, and King’s College London. Research by two coauthors was supported by NARSAD. The other authors and Dr Gonzalez report no relevant financial relationships.

Psychol Med. Published online November 29, 2015. Abstract

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