The popularity of cannabis-based products has risen sharply over the past ten years. One major reason is the 2018 federal decision to remove hemp from the Controlled Substances Act, which allowed hemp-derived CBD to be legally sold and widely distributed. As a result, CBD is now commonly available in oils, creams, and cosmetic items. It is widely accepted that CBD does not cause a 'high', but its effects within the human brain and body remain poorly understood. At this time, the Food and Drug Administration only approves CBD as an additional treatment for certain types of epilepsy, and it advises against its use during pregnancy.

"We need to understand more about this compound, what mechanisms it interacts with in the brain, its impact on the body, and whether it is a potentially safer solution for treating the chronic pain epidemic," said Kuan Hong Wang, PhD, professor of Neuroscience and member of the Del Monte Institute for Neuroscience at the University of Rochester. Working with researchers at Harvard Medical School and Boston Children's Hospital, Wang's lab recently showed in mice that they could deliver CBD directly to the brain to relieve neuropathic pain without producing harmful side effects. These results were published in Cell Chemical Biology.

A New Way to Deliver CBD to the Brain

The main obstacle for researchers was the blood-brain barrier, a protective system that shields the brain from harmful substances. While essential for brain health, this barrier significantly limits how much CBD can enter the brain, especially because CBD does not dissolve well in water. As a result, very little of the CBD taken in its usual oil form reaches the brain.

To address this challenge, staff scientist Jingyu Feng, PhD, the study's first author, helped create a specialized delivery method called inclusion-complex-enhanced nano-micelle formulation, or CBD-IN. This approach encloses CBD molecules within water-soluble nano-micelles, which are considered safe for use in foods and medicines.

Tests in mice showed that CBD-IN triggered pain relief within half an hour. Importantly, the mice did not experience the common side effects often linked to conventional pain medications, such as problems with balance, movement, or memory. "The pain relief also lasted through repeated use," said Feng. "We did not see its effect wear off over time."

How CBD-IN Affects the Nervous System

With the help of imaging tools and genetic mapping, the researchers found that CBD-IN reduces excessive nerve activity in areas of the brain and spinal cord involved in processing touch and pain. This effect only appeared in regions experiencing abnormal activation, such as after a nerve injury. Healthy neurons were unaffected.

Another unexpected result was that CBD-IN did not rely on the well-known cannabinoid receptors (CB1 and CB2) typically involved when THC or other cannabis compounds act in the body. "Instead, CBD-IN seems to influence broader electrical and calcium signaling in nerve cells, offering a new way to control nerve hyperactivity without triggering the 'high' or dependency risks associated with traditional cannabinoids or opioids," Feng said.

Potential for Treating Chronic Pain and Other Brain Disorders

"The broader implication of this research is that nanotechnology can make natural compounds like CBD more effective and precise," said Wang, co-senior author of the study. "By enhancing brain delivery and targeting only disease-related neural overactivity, this strategy could open new doors for treating chronic pain and possibly other neurological disorders, such as epilepsy or neurodegenerative diseases, where abnormal nerve activity plays a central role."

This work was carried out through a collaboration involving the University of Rochester, Harvard Medical School, and Boston Children's Hospital. Additional contributors include Jessica Page, PhD, and Leeyup Chung, PhD, both co-first authors, and Zhigang He, PhD, co-senior author, from Harvard Medical School. Funding was provided by the National Institutes of Health and the Del Monte Institute for Neuroscience.

• Chronic pain appears to play a meaningful role in raising the risk of developing high blood pressure.
• How long the pain lasts and where it occurs both influence that risk, and part of the connection is explained by depression and inflammation.
• Researchers say the results underscore how important effective pain management can be for preventing and controlling high blood pressure, a major driver of cardiovascular disease and death.

Chronic Pain Linked to Rising Blood Pressure Risk

Chronic pain in adults may raise the likelihood of developing high blood pressure, and factors such as where the pain is located, how widespread it is, and whether a person also has depression appear to play important roles. These findings come from new research published today (November 17) in Hypertension, an American Heart Association journal.

An evaluation of health information from more than 200,000 adults in the U.S. showed that individuals who experienced chronic pain throughout their bodies had a higher chance of developing high blood pressure compared to those reporting no pain, short-term discomfort, or pain limited to one region.

"The more widespread their pain, the higher their risk of developing high blood pressure," said lead study author Jill Pell, M.D., C.B.E., the Henry Mechan Professor of Public Health at the University of Glasgow in the United Kingdom. "Part of the explanation for this finding was that having chronic pain made people more likely to have depression, and then having depression made people more likely to develop high blood pressure. This suggests that early detection and treatment of depression, among people with pain, may help to reduce their risk of developing high blood pressure."

Understanding High Blood Pressure and Its Dangers

High blood pressure and hypertension occur when blood presses too strongly against vessel walls, increasing the chance of heart attack or stroke. High blood pressure, including stage one or stage two hypertension (blood pressure readings from 130/80 mm Hg to 140/90 mm Hg or higher), affects nearly half of adults in the U.S. It is also the leading cause of death nationally and worldwide, according to the 2025 joint American Heart Association/American College of Cardiology guideline endorsed by 11 other organizations.

Earlier studies show that chronic musculoskeletal pain -- pain in the hip, knee, back or neck/shoulder that lasts for at least three months -- is the most common form of long-term pain in the general population. The new study examined how the presence, type, and distribution of pain across the body relate to later high blood pressure.

Inflammation and depression are already recognized as contributing factors for high blood pressure; however, Pell noted that no previous research had evaluated how much these elements might explain the connection between long-lasting pain and future hypertension.

How Researchers Collected and Measured Pain Data

Participants completed a baseline questionnaire describing whether they had experienced pain in the previous month that interfered with daily activities. They identified whether the pain occurred in the head, face, neck/shoulder, back, stomach/abdomen, hip, knee or across the entire body. Those reporting pain also indicated whether symptoms had persisted for more than three months.

Depression was assessed through a questionnaire asking about depressed mood, disinterest, restlessness or lethargy during the previous two weeks. Inflammation was measured using blood tests for C-reactive protein (CRP).

Key Findings After Long-Term Follow-Up

After an average follow-up period of 13.5 years, the results showed:

• Nearly 10% of all participants developed high blood pressure.
• Compared to people without pain, those with chronic widespread pain faced the greatest increase in risk (75% higher), while short-term pain was associated with a 10% higher risk and chronic pain in a single location was tied to a 20% higher risk.
• When looking at pain locations, chronic widespread pain was linked to a 74% higher risk of high blood pressure; chronic abdominal pain to a 43% higher risk; chronic headaches to a 22% higher risk; chronic neck/shoulder pain to a 19% higher risk; chronic hip pain to a 17% higher risk; and chronic back pain to a 16% higher risk.
• Depression (11.3% of participants) and inflammation (0.4% of participants) explained 11.7% of the connection between chronic pain and high blood pressure.

"When providing care for people with pain, health care workers need to be aware that they are at higher risk of developing high blood pressure, either directly or via depression. Recognizing pain could help detect and treat these additional conditions early," Pell said.

Expert Perspective on Pain, Inflammation and Hypertension

Daniel W. Jones, M.D., FAHA, chair of the 2025 American Heart Association/American College of Cardiology High Blood Pressure Guideline and dean and professor emeritus of the University of Mississippi School of Medicine in Jackson, Mississippi, said, "It is well known that experiencing pain can raise blood pressure in the short term, however, we have known less about how chronic pain affects blood pressure. This study adds to that understanding, finding a correlation between the number of chronic pain sites and that the association may be mediated by inflammation and depression."

Jones, who was not involved in the study, recommended further research using randomized controlled trials to explore how different pain management strategies influence blood pressure. He highlighted the importance of understanding how Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) such as ibuprofen may raise blood pressure.

"Chronic pain needs to be managed within the context of the patients' blood pressure, especially in consideration of the use of pain medication that may adversely affect blood pressure," said Jones.

Study Limitations and Participant Characteristics

The researchers noted that the study population mainly consisted of middle-aged or older white adults of British origin, which means the findings may not apply to people of other racial or ethnic backgrounds or younger age groups. Pain levels were self-reported, and the study relied on clinical diagnostic coding, a single pain assessment, and two blood pressure measurements.

How the Study Was Designed

Study details, background and design:

• The analysis used data from the UK Biobank, a large population-based project that recruited more than 500,000 adults ages 40-69 between 2006 and 2010. Participants lived in England, Scotland and Wales.
• This study focused on 206,963 adults. The average age was 54 years; 61.7% were women, and 96.7% were white adults.
• Overall, 35.2% of participants reported chronic musculoskeletal pain; 62.2% reported chronic pain at one body site; 34.9% had chronic pain at two to three musculoskeletal sites; and 3.2% reported pain at four sites.
• Compared with participants without pain, those reporting pain were more often women, had less healthy lifestyle patterns, larger waist circumference, higher body mass index (BMI), more long-term health issues, and were more likely to live in areas with higher unemployment, lower home and car ownership, and more overcrowding.
• Researchers adjusted for factors associated with both pain and high blood pressure, including self-reported smoking status, alcohol intake, physical activity, sedentary time, sleep duration, and fruit and vegetable consumption.
• Data from the UK Biobank was gathered through a touch-screen questionnaire, interview, physical measurements (height, weight, BMI, waist circumference, blood pressure), and blood samples for cholesterol and blood sugar (hemoglobin A1c).
• Hospital records were used to identify high blood pressure using standard International Statistical Classification of Diseases and Related Problems and diagnostic codes (ICD-10 codes).
• The follow-up period was measured from baseline until one of these events occurred: a diagnosis of high blood pressure, the participant's death, or the end of available follow-up records. The first of these events marked the end of follow-up for each participant.