Naturally Produced Cannabinoids for Neuroprotection From Concussion

Naturally Produced Cannabinoids for Pain Management and Neuroprotection From Concussion During Participation in Contact Sports: Neuroprotection

The goal of this double-blind, placebo-controlled, cross over study is to learn about the neuroprotective properties of a broad-spectrum cannabinoid formulation in normal healthy adults engaged in elite contact sport competition.

The main question it aims to answer :

• Is the broad-spectrum cannabinoid formulation neuroprotective for athletes participating in competitive contact sports? Can this formulation facilitate recovery in those who suffer from concussion by reducing inflammation and/or reduce the number of concussions sustained without adverse physiological and psychological dysfunction when administered daily?

Participants will:

• be given a broad-spectrum cannabinoid gel capsule or a placebo twice daily.
• have blood samples taken to analyze pharmacokinetics and pharmacodynamics of cannabinoid metabolites, liver function, complete blood count and blood differential, inflammatory biomarkers and genetic analysis
• have stool samples collected for gut microbiome analysis;
• undergo testing sessions, which will include psychological and health questionnaires, equipment to record signals from the brain and heart, and safety laboratory tests.

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Broad spectrum cannabinoid formulation; Other: Placebo gel capsule

Detailed Description

This research project will be a Phase II clinical trial to test the neuroprotective properties of the broad spectrum cannabinoid formulation. Specifically, the investigators will assess the neuroprotective properties of the cannabinoid formulation during a competitive season of contact football or ice hockey in elite university varsity athletics.

The primary research hypothesis is that the cannabinoid formulation will be neuroprotective for athletes in a competitive university varsity football or hockey season and will help to reduce the number of concussions sustained by the athletes in comparison to previous seasons, and in comparison, to the Placebo group. Furthermore, it is expected that the cannabinoid formulation will facilitate recovery in those who do suffer from a concussion by reducing inflammation.

The secondary hypotheses are:

1. The cannabinoid formulation will result in improved physiological and psychological performance throughout the competitive season compared to placebo.
2. The inflammatory markers will be reduced in those taking the cannabinoid formulation as compared to those taking placebo.

This research study is unique and important for several reasons:

1. The investigators will conduct the first ever randomized controlled trial to understand the neuroprotective effects of a cannabinoid formulation designed to mitigate concussion in a population at a heightened risk of concussion and understand if recovery with the cannabinoid formulation more rapidly improves concussion symptoms.
2. The investigators will use an integrated approach to examine the effects of our cannabinoid formulation on qualitative and quantitative outcome measures including clinical, physiological, neurophysiological, biopsychological, and functional motor performance.
3. The cannabinoid levels will be studied in the blood to assess the pharmacokinetics and pharmacodynamics of these compounds and correlate these with our cerebrovascular, cardiovascular and neurophysiological indices.
4. The investigators will genotype participant blood samples for known polymorphisms (single nucleotide polymorphisms, copy number variants, etc.) and relate our findings to observed drug effect in study participants.
5. The investigators will investigate the effects of the cannabinoid formulation on the gut microbiome from stool samples, which has been implicated to have an effect on concussion.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Patrick Neary, Ph.D; Phone Number: 306-585-4844; Email: Patrick.Neary@uregina.ca
• Study Contact Backup: Name: Elizabeth S. Thompson, Ph.D; Phone Number: 708-774-7698; Email: e.thompson@usask.ca

Study Locations

• Canada
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4S-0A2
      • Recruiting
      • University of Regina
      • Contact: Patrick Neary, Ph.D; Phone Number: 306-585-4844; Email: Patrick.Neary@uregina.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy male adults between 19-35 years of age that compete in contact sport athletics.
• Participants with no known cerebrovascular or cardiovascular complications.
• Participants will not be habitual recreational users of cannabis (i.e., <1 day/week) or tobacco users.
• Participants that agree not use any other cannabis or tobacco products while enrolled in the study.
• Participants willing to provide a list of any prescription medications they are taking.
• Ability to maintain commitment to all proposed biopsychological and health questionnaires, and neuro-physiological, physiological, perceptual-cognitive, and functional motor skills laboratory tests.
• Participants who are capable of giving signed informed consent.

Exclusion Criteria:

• Female.
• Must not travel to the USA during study period; USA laws do not permit cross border with cannabis products.
• Use of cannabis-based therapy within 2 months (participants who have previously used a cannabis based therapy may be included if they have a 2-month period without use of cannabis-based therapy prior to enrollment in the study).
• Participants with any level of cannabis in their blood samples when sampled at the commencement of the study will be excluded.
• Participants that are being medically supervised for anxiety, depression, Post Traumatic Stress Disorder (PTSD), mood disorder, psychotic disorders or any cerebrovascular and cardiovascular complications.
• Participants who are taking prescription medications such as psychotropic medications with serotonergic activity, including Selective Serotonin Reuptake Inhibitors (i.e. Fluoxetine), Tricyclic Antidepressants (i.e. Elavil, Nortriptyline) and Atypical Neuroleptics (i.e. Risperidone, Seroquel).
• Initiation or dosage change of oral or injected steroids within 3 months.
• Allergy or known intolerance to any of the compounds within the study preparation.
• Unable to maintain commitment to all proposed biopsychological and health questionnaires, and neuro-physiological, physiological, and functional motor skills laboratory tests.
• Inability of study participants to attend assessments on a regular basis at the pre-determined times, or failure to take the drug daily.
• Clinically significant cardiac, renal or hepatic disease (as assessed by the site investigator).
• If they already have a concussion at the time of starting the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Broad sprectrum cannabinoid gel capsule; Gel capsule containing broad spectrum cannabinoid formulation	Drug: Broad spectrum cannabinoid formulation; Broad spectrum cannabinoid formulation gel capsule
Placebo Comparator: Placebo; Placebo gel capsule	Other: Placebo gel capsule; Placebo gel capsule will have MCT oil only, no active ingredient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma cannabidiol (CBD) metabolite concentration	Change in plasma concentrations of cannabidiol (CBD) and CBD metabolites measured from venous blood samples.	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Plasma tetrahydrocannabinol (THC) metabolite concentration	Change in plasma concentrations of tetrahydrocannabinol (THC) and THC metabolites measured from venous blood samples.	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Inflammatory biomarker concentrations in blood	Change in blood concentrations of inflammatory and neurobiological biomarkers, including tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP), measured from venous blood samples.	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Liver function laboratory values	Change in liver function laboratory values, including total protein, albumin, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), measured from venous blood samples at a provincial accredited laboratory.	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Hematology and clinical chemistry laboratory values	Change in complete blood count, blood differential, sodium, potassium, chloride, total CO2, calcium, magnesium, phosphate, and creatinine measured from venous blood samples.	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Cerebral blood flow velocity	Change in cerebral blood flow velocity in the middle cerebral artery and posterior cerebral artery measured by transcranial Doppler ultrasound.	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Cerebral oxygenation	Change in cerebral oxygenation in the right and left prefrontal cortex measured by functional near-infrared spectroscopy.	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Continuous blood pressure	Change in continuous blood pressure measured using Finapres Nova finger photoplethysmography.	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Changes in cardiovascular physiology	Change in cardiac cycle timing parameters measured using seismocardiography (SCG).	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Officially diagnosed concussion incidence	Number of officially diagnosed concussions sustained by participants during the study period.	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortical inhibition measured by transcranial magnetic stimulation (TMS)	Monitor excitatory:inhibitory ratio of neurotransmitter activity via transcranial magnetic stimulation (TMS) including cortical silent period and short-interval intracortical inhibition.	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Brief Pain Inventory-Short Form Pain Interference score	Change in pain interference measured using the Brief Pain Inventory-Short Form (BPI-SF) Pain Interference Scale. The Pain Interference score is calculated as the mean of seven items assessing interference with general activity, mood, walking ability, work, relationships, sleep, and enjoyment of life. Scores range from 0 to 10, with higher scores indicating greater pain interference. Units: 0-10 scale score	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Brief Pain Inventory-Short Form Pain Severity Score	Change in pain severity measured using the Brief Pain Inventory-Short Form (BPI-SF) Pain Severity Scale. The Pain Severity score is calculated as the mean of four items (worst, least, average, and current pain). Scores range from 0 to 10, with higher scores indicating greater pain severity. Units: 0-10 scale score	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
McGill Pain Questionnaire-Short Form pain score	Change in pain measured using the Short-Form McGill Pain Questionnaire (SF-MPQ). The questionnaire includes 15 pain descriptors (11 sensory and 4 affective), each rated from 0 (none) to 3 (severe). The total score ranges from 0 to 45, with higher scores indicating greater pain severity. Units: 0-45 scale score	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Numeric Rating Scale for Pain score	Change in pain intensity measured using the Numeric Rating Scale (NRS). Participants rate their pain on an 11-point scale from 0 to 10, where 0 indicates no pain and 10 indicates the worst pain imaginable. Higher scores indicate greater pain intensity. Units: 0-10 scale score	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants.
Pain Behaviour Measurement score	Change in observed pain behavior measured using the Pain Behaviour Measurement (PBM) system. The PBM quantifies the frequency and/or duration of observed pain-related behaviors during standardized assessment. Higher scores indicate greater pain-related behavior. Units: PBM score	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Change in Leeds Sleep Evaluation Questionnaire (LSEQ) score	The LSEQ is a validated 10-item questionnaire that assesses getting to sleep, quality of sleep, awakening from sleep, and behaviour following wakefulness. Scores are reported on a 0 to 100 visual analogue scale, with higher scores indicating better perceived sleep quality and sleep-related functioning. Units: 0-100 scale score	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Vertical Jump Performance	Change in vertical jump height measured using the Vertec vertical jump test.	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Adverse Event Incidence	Number of participants experiencing adverse events, including sleepiness, lethargy, irritability, nausea, vomiting, and diarrhea.	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Stool microbiome composition	Change in gastrointestinal microbiome composition assessed using stool sample analysis performed using standard laboratory methods.	From enrollment to end of treatment crossover (4 weeks for football participants or 8 weeks for hockey participants).
Identification of genetic markers associated with cannabinoid metabolism	Single nucleotide polymorphisms and copy number variants associated with inter-individual metabolic differences in cannabinoid metabolism identified using next-generation sequencing.	Baseline assessment.

Collaborators and Investigators

• Sponsor: University of Regina
• Collaborators: National Football League

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: June 23, 2026
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 21, 2026

Study Record Updates

• Last Update Posted (Actual): July 21, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: cannabis; inflammation; concussion; cannabinoid; cbd; hemp
• Additional Relevant MeSH Terms: Brain Injuries, Traumatic; Cone Dystrophy; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Wounds and Injuries; Pathologic Processes; Eye Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Eye Diseases, Hereditary; Vision Disorders; Sensation Disorders; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Inflammation; Brain Concussion; Marijuana Abuse; Color Vision Defects
• Other Study ID Numbers: Bio3456; NFL-NEUROPROTECTION-02 (Other Identifier: University of Regina)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No