Inflammation levels may shape how cannabis affects anxiety and sleep

A new study published in Frontiers in Behavioral Neuroscience suggests that baseline levels of inflammation may influence how cannabis affects mood and sleep in people with anxiety. Researchers found that cannabis products higher in cannabidiol (CBD) tended to produce more consistent improvements in negative mood and sleep quality, while the benefits of tetrahydrocannabinol (THC)-dominant products varied depending on participants’ inflammatory status.

Anxiety affects nearly one in three adults in the United States and often overlaps with other issues, such as poor sleep. Many individuals with anxiety experience insomnia or disrupted rest, which can in turn worsen mental health. Treatments for these conditions are often addressed separately, even though they frequently occur together.

Emerging evidence indicates that inflammation—a process in which the immune system releases chemical messengers called cytokines—may be a shared biological factor contributing to both anxiety and sleep problems. Higher cytokine levels have been linked to worse mood and poorer sleep quality in prior studies.

Cannabinoids like THC and CBD, found in the cannabis plant, are known to have anti-inflammatory effects in laboratory settings. Surveys also suggest that many medical cannabis users turn to the drug to help with anxiety and sleep issues. However, scientific findings on cannabis for these purposes remain mixed, and little is known about whether a person’s level of inflammation might influence the outcome.

The researchers sought to investigate whether four weeks of cannabis use would affect inflammatory markers in the blood, and whether baseline inflammation might change how cannabis influences mood and sleep quality. They also wanted to compare products with different cannabinoid profiles: THC-dominant, CBD-dominant, and those containing equal parts THC and CBD.

“Reducing anxiety and improving sleep are two of the most commonly reported reasons why people report using cannabis. And while it makes sense that anxiety and sleep might be linked (who hasn’t tossed and turned at night when they have a lot on their mind?), both are also rooted in inflammation,” said study author Jonathon K. Lisano, a postdoctoral research associate in the CUChange lab at the University of Colorado Boulder.

“Higher levels of inflammation, which is generally not great, have been linked to both higher levels of anxiety and worsened sleep quality. With cannabis, particularly CBD, being able to impact inflammation we wanted to see if there was a relationship between cannabis use, inflammation, anxiety, and sleep.”

The study included 171 adults with at least mild anxiety. Of these, 147 were assigned to use one of three types of cannabis—THC + CBD (12% each), THC-dominant (24% THC, very low CBD), or CBD-dominant (24% CBD, very low THC)—while 24 participants served as a non-use control group. Participants in the cannabis groups purchased their assigned products from a dispensary and used them as much or as little as they wished over the four-week period.

All participants completed questionnaires assessing depression, anxiety, stress, and sleep quality at the start of the study and after four weeks. Blood samples were collected at both time points to measure concentrations of six pro-inflammatory cytokines, which were combined into a single inflammation score. The researchers examined whether cannabis use changed cytokine levels and whether starting levels of inflammation influenced the effects of cannabis on mood and sleep.

Cannabis use did not significantly alter cytokine levels over the four-week period, regardless of the product type. “I was surprised to see that despite there being a decent amount of pre-clinical data on the anti-inflammatory effects of cannabis, we did not observe any changes in inflammation over the 4 weeks of this study,” Lisano told PsyPost. “This could be due to those pre-clinical studies using much higher doses of CBD and THC than is obtainable for the average individual using cannabis.”

However, initial inflammation levels played a notable role in shaping outcomes for mood and sleep. Participants using CBD-dominant or THC + CBD products experienced consistent improvements in overall negative mood scores—covering depression, anxiety, and stress—across all levels of baseline inflammation. These improvements were driven mainly by reductions in depression and anxiety, while stress levels showed little change.

In contrast, those using THC-dominant cannabis saw mood improvements only if their baseline inflammation was in the average range, with little or no benefit for participants with low or high inflammation. The non-use control group also showed some mood improvement, but it was less consistent and did not appear tied to changes in specific mood components.

Sleep quality showed a similar pattern. Cannabis users with average or high baseline inflammation tended to report better sleep after four weeks, particularly if they used CBD-rich products. For participants with low inflammation, improvements were smaller and less consistent. Those who did not use cannabis reported no meaningful changes in sleep quality regardless of their inflammation level.

The researchers suggest that CBD’s more consistent effects could be linked to its stronger anti-inflammatory actions compared to THC. Laboratory studies indicate that CBD may reduce the release of inflammatory cytokines by influencing pathways in immune cells, potentially stabilizing mood and sleep regulation across different inflammatory states.

“I think my big takeaways from these results are twofold,” Lisano explained. “1. Inflammation does appear to impact how cannabis affects our sleep and anxiety over time (which is the first time this has been reported). 2. Products containing higher amounts of CBD appeared to produce the most consistent reductions in anxiety and improvements in sleep quality. Products containing high amounts of THC had varied results, especially when it came to sleep.”

The study’s design had strengths, including a naturalistic approach that reflected real-world cannabis use and verification of product adherence through blood tests. However, the absence of a placebo control means some of the reported benefits could reflect participants’ expectations rather than purely pharmacological effects. Federal restrictions in the United States make placebo-controlled studies with legal-market cannabis challenging.

The results are also limited to smoked or vaporized cannabis flower and may not apply to edibles, tinctures, or concentrates. Additionally, the study only covered a four-week period, so it is unclear whether the effects would persist, diminish, or change with longer-term use.

“I think the big thing people need to keep in mind is that these results are preliminary; one study is not the end-all be-all when it comes to the impact of cannabis on sleep and anxiety,” Lisano noted. “While we report that sleep quality got better over the 4 weeks, this is based on the participant’s subjective experience. Just because we feel like we are sleeping better doesn’t mean we actually got better sleep. There still needs to be more research using more objective data (i.e., sleep studies looking at sleep cycles and brain wave activity).”

The authors note that future studies should examine how dose, frequency, and method of cannabis use interact with inflammation to influence mood and sleep. Longer-term research could also determine whether these benefits hold for individuals with more severe, clinically diagnosed anxiety disorders.

“I’m hoping we can start to look at a few different things,” Lisano said. “It would be great to look at more objective data regarding sleep quality to assess if people are actually getting better quantifiable sleep versus just feeling like they are sleeping better. It would also be great to see what other aspects of health, like exercise, diet, etc., influence the effects of cannabis on things like anxiety, sleep, and pain.”

The study, “Inflammatory state moderates response to cannabis on negative affect and sleep quality in individuals with anxiety,” was authored by Jonathon K. Lisano, Carillon J. Skrzynski, Gregory Giordano, Angela D. Bryan, and L. Cinnamon Bidwell.