This week's lead article, Blood pressure drug shows promise in preventing posttraumatic headaches, is in the Therapies & Diagnostic Tools Under Research category.

a bottle of the medication Prazosin on a blue background

In this newsletter: Opportunities, Cannabis & Psychedelics, Self Care, Therapies & Diagnostic Tools Under Research, Mental Health, and Women’s Health

We appreciate the Concussion Alliance interns and staff members who created this edition:
Writers: Alexander Rosmarino, Kira Kunzman, Charley Draheim, Mackenzie Keesor, and Hannah Hartmann

Editors: Kira Kunzman, Conor Gormally, and Malayka Gormally

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Opportunities

a group of elementary school children up a flight of stairs into a school building

Podcast about the 6th International Consensus on Concussion in Sport: No more cocooning! Return to school and sport after sports-related concussion, with Prof John Leddy and Dr. Margot Putukian, presented by the British Journal of Sports Medicine. The podcast description includes links to five of the systematic reviews that informed the decision-making process for the 6th Consensus. Also available on Apple Podcasts.

Cannabis & Psychedelics

CBD and THC found in cannabis show promise for treating anxiety disorders

two cannabis leaves with the words THC on the left and CBD on the right

A study published in the Sage Journals finds that two major components in cannabis–CBD and THC–are effective in treating patients with anxiety disorders. The study, by Sophie K. Stack et al., is an interim analysis of an ongoing observational study conducted by medical cannabis prescribers in Australia. They followed 568 candidates across an average observational period of 154 days; an additional 198 participants were also used for effectiveness analysis. Study participants were divided into two groups: PTSD and unspecified or other anxiety disorders. The authors also split participants into groups by type of cannabis used: CBD-only formulas, THC-only formulas, those with a balanced formula, and those with a CBD or THC-dominant formula. In the study, “‘Dominant’ refers to a concentration of 1 constituent that is 1.5-times greater than the other.”

The median doses throughout the study were 50.0 mg/day of CBD and 4.4 mg/day of THC. Overall, CBD was associated with the most significant effect on anxiety outcomes across all measured daily life domains in all participant groups. Unexpectedly, those prescribed the THC-dominant formulation reported substantial decreases in anxiety levels and the highest proportion of clinical improvement, although this THC-dominant formula was associated with a reduction in participants’ ability to participate in social roles and activities.

The effectiveness of the formulas was based on outcomes in seven domains: physical function, fatigue, sleep disturbance, depressive symptoms, anxiety, ability to participate in social roles and activities, and pain interfering with daily life. CBD-only was the most effective formulation type and improved four domains for all participants: anxiety, depression, fatigue, and the ability to participate in social activities. In participants with PTSD, the CBD-only formula was the “only formulation associated with significant decreases in anxiety and depression,” and was associated with most-improved outcomes. Symptoms of depression in the PTSD group were also significantly more likely to be classified as clinically improved for those taking the balanced formulas.

For all participants (unspecified anxiety disorder and PTSD), both the CBD-dominant and balanced formulas were associated with improvements in anxiety. The CBD-only formula contained four times more CBD than the CBD-dominant formula and five times more CBD than the balanced formula. The balanced and CBD-dominant formulas produced almost equal improvements in anxiety compared to the CBD-only formula, with these formulas having significantly lower doses of CBD. This finding suggests that lower doses of CBD could be as effective as higher doses or that there are diminishing returns to CBD’s anxiolytic (anxiety-reducing) properties.

Surprisingly, the THC-dominant formulation resulted in significant decreases in anxiety levels and the highest proportion of clinical improvement, although participants taking this formula reported a decline in their ability to participate in social roles and activities. This result was unexpected; other research had indicated that doses higher than 30 mg/day of THC would be anxiogenic, but the median THC dose in the THC-dominant formulation was 33.8 mg/day. A previous study found that doses of CBD from 15-60 mg/day could offset THC’s anxiogenic (anxiety-increasing) properties. This offsetting effect of CBD was present in this study in the balanced and THC-dominant groups. The THC-dominant formulation included a median of 6.0 mg/day of CBD, so a much lower CBD dose created the THC offsetting effect than previous study findings.

Overall this study proved that there is still much to learn about the world of cannabinoids and medicinal cannabis. This test was relatively small, and a larger sample size is still needed to better understand these compounds’ effects and mechanisms.

Self Care

Moderate to vigorous physical activity linked to faster symptom recovery in adolescents

the lower legs of a woman running on a treadmill

Engaging in daily moderate to vigorous physical activity (MVPA) during the 7-14 days following a concussion is associated with a faster symptom recovery time, according to a recent study published in the Journal of Sports Medicine. Researchers Rademacher et al. examined 54 adolescents’ activity levels following a diagnosed concussion to determine whether sedentary time, light activity time, MVPA time, or activity frequency had the largest effect on symptom resolution. They found that the optimal intensity and frequency of physical activity (PA) for concussion recovery was moderate to vigorous PA for 30 or more minutes daily during the subacute stage of concussion recovery (within 14 days post-concussion). Sedentary time, light activity time, and activity frequency were not associated with quicker recovery time.

Clinicians should consider encouraging patients in the subacute phase of concussion recovery to safely engage in daily MVPA for longer periods. An additional assessment of sex differences between the participants found that female participants typically engaged in more sedentary time than male participants. The study speculates that these findings could shed light on the differences in recovery time and symptom presentation between female and male sex. However, more research is necessary to support this conclusion.

The study analyzed the physical activity of 54 adolescents (ages 10-18) assessed within 14 days after experiencing a concussion. Participants reported the type and severity of their symptoms using a Post-Concussion Symptom Inventory (PCSI) at the beginning and throughout the progression of the study. Participants wore an activity tracker on their wrists constantly–which reported their heart rate zones throughout the day–for one week following enrollment. The heart rate zones categorized the activity levels: “sedentary (below 50% of age-predicted max heart rate), light physical activity (50%-69% of age-predicted max heart rate), and MVPA (70-100% of age-predicted max heart rate)” For each of these categories, the authors calculated the average time (in minutes) spent in each activity level per day. Activity frequency was measured by “the number of hours per day a participant took more than 250 steps.” Although no participants were given specific physical activity recommendations, their clinicians may have advised them about what kinds of activity to do.

While this study sheds light on concussion in adolescents and some possible variables contributing to differences in the male and female recovery process, further research should examine these findings with younger and older populations. Additionally, alternative measures of activity levels may be beneficial, as a wrist-worn tracker only tracks heart rate and not the type of activity or other relevant aspects.

Therapies & Diagnostic Tools Under Research

Blood pressure drug shows promise in preventing posttraumatic headaches

a bottle of generic medication, Prazosin, against a blue background

The blood pressure drug prazosin can effectively reduce posttraumatic headaches, as demonstrated in a recent study published in the Journal of Headache and Pain. An article from the U.S. Department of Veterans Affairs discusses the prazosin study, noting the lack of treatment options for posttraumatic headaches–a common long-term consequence of mild traumatic brain injuries in Veterans and service members. The study investigates the potential effectiveness of prazosin as a treatment option for these headaches, aiming to provide better solutions for those affected. While more extensive clinical trials are needed to confirm these promising results, the fact that prazosin is already widely used and familiar to healthcare providers in the VA and Department of Defense makes it a potential evidence-based approach to alleviate the suffering of individuals with posttraumatic headaches.

Prazosin, an FDA-approved drug for hypertension, was evaluated in a placebo-controlled randomized control trial to assess its impact on reducing the frequency and severity of posttraumatic headaches. Researchers from the VA Puget Sound Health Care System conducted this pilot trial with 48 Veterans and service members experiencing headaches due to mild traumatic brain injury. The participants were randomly split into a 32-participant prazosin experimental group and a 16-participant placebo control group. The prazosin group received gradually increasing doses of prazosin for five weeks, followed by the maximum dose for 12 weeks. The results revealed that prazosin was well-tolerated, with morning drowsiness being the only reported adverse effect.

Before the trial, the participants in the prazosin group experienced an average of 18.3 headache days per month, and at the end of 12 weeks, their headaches had decreased to six days per month. In contrast, the placebo group participants initially experienced 18.6 headache days per month, which dropped to 12 days at the end of the trial. Moreover, 70% of those taking prazosin had at least a 50% reduction in their headache frequency by the end of the 12 weeks, while only 29% in the placebo group experienced the same level of improvement. Participants taking prazosin reported a significant improvement in the impact of headaches on their daily functioning compared to the placebo group.

With limited treatment options available, the effectiveness of prazosin in reducing headache frequency and improving quality of life brings hope to those struggling with posttraumatic headaches. The lead author of the study, Dr. Murray Raskind, explained the significance of the research, stating, “Persistent posttraumatic headaches are the most common long-term consequence of mild traumatic brain injuries (concussions) in Veterans and active-duty service members, causing substantial distress and disability at home and work. Although these headaches resemble migraine headaches symptomatically, they often fail to respond to the prevention treatments useful for migraines.”

However, as reported in the study, it’s essential to be aware of potential side effects and adverse events associated with prazosin use. Patients should consult with their healthcare providers to weigh the benefits and risks before considering prazosin as a treatment option. The research highlights the need for careful monitoring and individualized care to ensure the best possible outcomes for those seeking relief from posttraumatic headaches. This study lays the foundation for further research into using prazosin and may lead to improved management strategies for this common condition many Veterans and service members face.

Mental Health

Schools are an ideal location to promote mental health and well-being, but must take into account social inequalities

young woman, with her hands on her forehead, at her desk in a classroom filled with students

Schools are an ideal location to aid in nurturing students’ mental health and well-being. However, social and perceived inequalities present challenges in creating school-based interventions meant to address the well-being of all students. In a recently published article, Mansfield et al. determined that students from more disadvantaged homes would benefit the least from common universal school-based interventions. Published in JCPP Advances, their study notes that universal approaches tend to aim to change outcomes using a one-size-fits-all approach. This approach does not work for the most vulnerable students, who could often benefit the most from interventions designed with them in mind. School-based interventions must work against the enforcement of inequalities and actively work towards reducing them. A more tailored intervention–known as selective intervention–may be more effective for at-risk students but has other drawbacks, including inducing stigma and consequently increasing perceived inequalities.

The study authors suggest that intervention design should address inequalities with understanding and consider multiple risk factors and mechanisms. One priority should be assessing needs via appropriate research about the student population. It is vital that any school-based intervention incorporates research data with diverse and representative sampling. After identifying accurate data about the student population the intervention will serve, addressing the population’s needs is done most effectively with combined intervention types, maximizing the number of issues the intervention can address.

To maximize engagement and inclusivity, each student must have access to and opportunities to complete the school-based interventions. Additionally, the study authors suggest that working with an inclusive group of students would help determine which components and ideas work best for meeting the intervention goals. Including students in choosing specific activities they will complete promotes agency and ensures perceived inequalities are not reinforced by assigning particular students to specific tasks.

Women’s Health

Females have disrupted brain activity that is not present in males following pediatric concussion

A medical technician preparing a woman to be put into a MRI machine

Researchers published the first study examining sex differences in resting state functional brain activity (rs-fMRI) for pediatric concussion patients. Research by Bhanu Sharma et al. published in Scientific Reports found that one month following injury, female patients had significantly more disruptions in brain activity when compared to males. The study authors suggest that females have a longer recovery time and that return-to-sport guidelines should vary by sex. They also imply that the hypothalamic-pituitary-ovarian axis, which influences hormone production, may be one of the reasons females have persisting differences in functional connectivity. Access our resources to learn more about hormone dysfunction following concussion and concussion in women and girls.

The research team observed significant differences in female concussion patients one month post-injury. There was increased (hyper-) connectivity in 4 brain regions (cuneal cortex, cerebellum, cuneal cortex, default mode network) and reduced (hypo-) connectivity between the temporal brain structures and the occipital region. In addition, the female patients had hypo- and hyper-connectivity in 10 and 5 significant clusters, respectively. In the male concussion patients, there were only three clusters of hypo-connectivity: in the frontal and medial brain structures, as well as in the occipital lobe.

Sharma et al. conducted a secondary data analysis examining 29 children recruited from McMaster University between 9 and 17 with a current concussion diagnosis and similar levels of persisting symptoms–as measured by the Post-Concussion Symptom Scale (PCSS). They used rs-fMRI’s to measure connectivity between brain regions and compared this data to data from 361 healthy controls obtained through a brain imaging data exchange database.

This study is the first to find differences in brain activity between sexes following pediatric concussion. Future studies should include longitudinal assessments to examine the relationship between concussion symptoms and rs-fMRI results, as well as the acute vs. chronic stages of injury and rs-fMRI activity.