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Exposure to cannabis cues increases brain activity among cannabis users, possibly triggering cravings

A systematic review published in the journal Psychopharmacology found elevated brain reactivity to cannabis cues among regular cannabis users, in specific brain regions. The study also uncovered preliminary evidence that this increased brain function may trigger cannabis cravings.

Cannabis is one of the most commonly consumed drugs around the world. As cannabis becomes increasingly legalized, the substance is being more heavily marketed and made available. This may be troubling, given evidence that regular cannabis use can lead to cannabis use disorder and other psychosocial outcomes like lower IQ and poorer cognitive performance.

There is interest in developing intervention strategies to mitigate these negative effects, yet the neural processes associated with cannabis use remain poorly understood. One consistent finding is that regular cannabis users show increased reactivity to cannabis-related cues, like smells or paraphernalia. Drug-cue reactivity studies for other substances suggest that this increased reactivity is due to the sensitization of reward pathways in the brain. If these reward pathways are being activated during exposure to cannabis cues, this could potentially trigger cravings or relapse among users hoping to quit.

“I lead the Neuroscience of Addiction and Mental Health Program at the Healthy Brain and Mind Research Centre at Australian Catholic University,” said study author Valentina Lorenzetti. “One of our focuses is to understand the neurobiological mechanisms of substance use and related disorders, using neuroimaging tools that take pictures of the brain in-vivo and with a high-resolution.”

“How the brain processes reactivity to cannabis cues is important and fitting to our agenda, so we can better understand the neural mechanisms that may drive people’s cannabis related cravings. This topic was the focus of our PhD student Hannah Sehl, who has a master in clinical psychology and is equipped to approach the topic from a scientific and clinical angle.”

“The topic is very timely given the global trends to decriminalization of medicinal and non-medicinal cannabis, people are exposed to more ads of cannabis products, shops with cannabis products,” Lorenzetti said. “On the other side, we know that cannabis cues in the environment – such as images of cannabis, a shop with cannabis, someone using cannabis – can trigger people to want to use and crave cannabis because of impulse or habit. In vulnerable people, these cravings may make it difficult to cut down their use or to stay abstinent. It is like when you are not hungry but then see an ad of pizza and fries, you end up craving them, and before you know it you end up in a shop to buy them and eat them.”

Lorenzetti and her colleagues conducted a systematic review of the related literature. Specifically, they analyzed 18 studies that used functional magnetic resonance imaging (fMRI) to examine brain function in cannabis users during exposure to cannabis cues (vs. neutral stimuli). Twelve studies were conducted among cannabis users only, and 8 studies were conducted with cannabis users and controls. The studies included a total of 918 participants — 603 cannabis users and 315 control subjects.

In their summary of the data, the researchers report that 11 of the 12 studies conducted on only cannabis users found heightened brain reactivity to cannabis cues compared to neutral stimuli. This heightened reactivity was most consistently found in the hippocampus/parahippocampus and amygdala. Seven of the 8 studies that included a control group found that cannabis users showed greater reactivity to cannabis cues versus neutral cues when compared to non-cannabis users. This elevated activity tended to occur in the striatum, the prefrontal cortex, and the parietal cortex — addiction-relevant pathways. Notably, these brain regions overlap with areas found to be implicated in reward processing among cannabis users.

“The findings from the scientific literature confirm that when people who use cannabis see cannabis related cues (such as images, paraphernalia, smells), they can be triggered to experience more cannabis craving,” Lorenzetti told PsyPost. “If you are aware that you are reacting to triggers, seek professional help! Many empowering and effective strategies exist that can help successfully manage cannabis cravings, how to deal with being surrounded with cannabis ads and shops, and to become more tolerant of discomfort and craving. ”

Interestingly, 13 of the studies reported on associations between brain activity and subjective cannabis craving. While these findings were somewhat mixed, certain brain areas were more consistently linked to cravings — the dorsal striatum, the orbitofrontal cortex, the amygdala, and the insula. The study authors noted that these brain areas partially overlap with regions found to be differentially activated among cannabis users (vs. non-users) during exposure to cannabis cues. This may suggest that altered brain reactivity is responsible for triggering higher subjective cravings with exposure to cannabis cues.

“The findings confirm that there are objective differences in how the brain processes cannabis related cues, and in some people this may drive how much they are craving,” Lorenzetti explained.

The study authors expressed that their review was based on cross-sectional data, and that future longitudinal studies are needed. This would allow researchers to investigate how brain activation during cannabis cue exposure may change as a person’s cannabis use increases or decreases.

“Now that we have established that cannabis use can trigger cravings and brain changes in people who use cannabis, we are trying to find how to mitigate or eliminate such brain reactivity in people who seek treatment and are vulnerable to relapsing, or in those who want to gain greater control over their use,” Lorenzetti said.

“More studies are required to understand how people react to cannabis cues, changes depending on whether they do or don’t experience problems with their cannabis use, and after they quit cannabis for good. We also don’t know if people who use cannabis for medical purposes report similar experiences.”

“More scientific evidence is required to compare how people react to cannabis and to other stimuli that can also be rewarding – such as high calorie foods, or shopping websites,” Lorenzetti continued. “Is the literature showing these brain changes because studies did not use comparison stimuli that were used, are attractive enough?”

Despite the need for more research, the new findings have some practical implications.

“If you are a health professional, you may account in the treatment plan for the fact that seeing cannabis cues can increase craving,” Lorenzetti said. “Also, policy makers that regulate how cannabis products are advertised may account for the fact that people can react to cannabis images with cravings, and vulnerable people may relapse.”

The study, “Patterns of brain function associated with cannabis cue-reactivity in regular cannabis users: a systematic review of fMRI studies”, was authored by Hannah Sehl, Gill Terrett, Lisa‑Marie Greenwood, Magdalena Kowalczyk, Hannah Thomson, Govinda Poudel, Victoria Manning, and Valentina Lorenzetti.

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