Proof of Concept Trial of Cannabis Derivatives in Neuropathic Pain (CAN)

February 23, 2026 updated by: VA Office of Research and Development
Chronic neuropathic pain (CNP) is disabling. Research on frontline treatments for CNP, shows inconsistent outcomes and dissatisfaction among Veterans. Veterans and clinicians have shown significant interest in cannabis derivatives (THC, CBD) for neuropathic pain control, but there are no well-controlled trials guiding expectations for benefit and adverse outcomes associated with cannabis for CNP. Because Veterans are likely to present with pain and pain-related polymorbidity significantly differing from that of civilians, a well-structured clinical trial of cannabinoids for Veterans with CNP is vital.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Chronic pain is a significant burden to United States Veterans and is a particular concern for Veterans. One of the causes of pain is chronic neuropathic pain (CNP). Frontline treatment for CNP, show inconsistent outcomes and have significant side effects. The ongoing opioid crisis has led to significant interest in safe and effective alternatives for pain control, and there is a significant need for research on desirable options for pain control that are likely to improve treatment adherence and outcomes. Veterans groups and Veterans Affairs clinicians have expressed significant interest in cannabis and its principal constituents (delta-9-tetrahydrocannabinol, THC; cannabidiol, CBD) for pain management, but the extant research describing the potential risks and benefits of cannabis for pain is weak. This randomized trial was developed as a proof of concept study to determine if cannabis constituents (THC, CBD, and THC+CBD) are superior to placebo in reducing pain in Veterans with CNP. The study is to recruit a sample of 320 adult Veterans who meet diagnostic criteria for high-impact CNP, are on stable treatment(s) for CNP, are not current cannabis users and who do not meet diagnostic criteria for Cannabis Use Disorder. This randomized phase II, 4-arm clinical trial aims to determine if cannabis constituents (THC, CBD) or their combination (THC+CBD) are superior to placebo in reducing pain in Veterans with CNP. This trial will offer the first evidence describing the potential benefits and adverse effects of cannabinoids for CNP in Veterans.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
320

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92161-0002
        • Recruiting
        • VA San Diego Healthcare System, San Diego, CA
        • Contact:
      • West Los Angeles, California, United States, 90073-1003
        • Active, not recruiting
        • VA Greater Los Angeles Healthcare System, West Los Angeles, CA
    • Connecticut
      • West Haven, Connecticut, United States, 06516-2770
        • Recruiting
        • VA Connecticut Healthcare System West Haven Campus, West Haven, CT
        • Principal Investigator:
          • Deepak D'Souza, MD MBBS
        • Contact:
    • Rhode Island
      • Providence, Rhode Island, United States, 02908-4734
        • Recruiting
        • Providence VA Medical Center, Providence, RI
        • Contact:
    • Texas
      • San Antonio, Texas, United States, 78229-4404
        • Recruiting
        • South Texas Health Care System, San Antonio, TX
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98108-1532
        • Terminated
        • VA Puget Sound Health Care System Seattle Division, Seattle, WA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Able to provide written consent
  • Veterans 21 years and older at the date of screening
  • Meet diagnostic criteria for neuropathic pain as defined by the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG)
  • Meet criteria for persistent, high-impact pain criteria.
  • Presence of allodynia confirmed by one of the screening dynamic brush tests
  • women of childbearing potential who agree to abide by contraceptive requirements

Exclusion Criteria:

  • Actively engaged in or planning to enter a program of non-pharmacological invasive intervention for pain at the time of enrollment
  • Peripheral neuropathy is not a primary source of neuropathic pain
  • Hypersensitivity to THC, CBD, or THC/CBD
  • Self-report of cannabis use during screening phase confirmed by positive urine toxicology for THC-COOH as measured and resulted at visit 5 before randomization
  • Unwilling to refrain from using cannabis or cannabis-based products through the entire duration of the study
  • Diagnosis of DSM-5 Cannabis Use Disorder in the past 6 months
  • Current DSM-5 diagnosis of cannabis use disorder, substance use disorder or serious psychiatric disorders
  • Actual change or intent to change is greater than a 20% change (increase or decrease) in any other medication for pain or non-pharmacological treatment from 4 weeks before the screening appointment until completion of study (i.e., visit 13)
  • Opioid doses > 400 mg MME (morphine milligram equivalent)
  • Women who are pregnant or breastfeeding, or who intend to become pregnant in the 12 weeks from enrollment
  • Any current unstable or concerning medical condition that would place the patient at increased risk, including hepatic, respiratory, immunological, cardiovascular, endocrine, or renal disease, or in the opinion of the investigator, prevents adherence with the protocol
  • Need for immediate psychiatric hospitalization
  • Enrolled in a medical marijuana program
  • Federal employee

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: CBD (Epidolex)
Target dose of 800 mg per day.
Drug: Placebo
Placebo
Drug: CBD (Epidolex)
Participants will receive a target dose of 800 mg per day of CBD (Epidolex).
Active Comparator: THC + CBD (Nabiximols)
Target dose of 10.8 mg / 10 mg per day.
Drug: Placebo
Placebo
Drug: THC + CBD (Nabiximols)
Participants will receive a target dose of 10.8 mg / 10 mg per day of THC + CBD (Nabiximols).
Placebo Comparator: Placebo
Identical in appearance to the three active comparators.
Drug: Placebo
Placebo
Active Comparator: THC (Syndros)
Target dose of 10mg per day.
Drug: Placebo
Placebo
Drug: THC (Syndros)
Participants will receive a target dose of 10mg per day of THC (Syndros).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To compare the short-term efficacy of THC, CBD, or THC+CBD vs Placebo on Neuropathic Pain as measured by the Numeric Rating Scale of Pain
Time Frame: Baseline, Week 6
The mean change in the weekly average of daily Numeric Rating Scale (NRS) pain score (0-10 scale; 0=no pain, 10=worst possible pain) from baseline to week 6.
Baseline, Week 6

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in pain quality (allodynia) as measured by the Quantitative Sensory Testing.
Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8
Allodynia measured by Quantitative Sensory Testing (QST) (0-10 scale; 0=no pain, 10=worst possible pain)
Baseline, Week 2, Week 4, Week 6, Week 8
To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in disability and function as measured by the Neuropathic Pain Scale.
Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8
Neuropathic Pain Scale (NPS) total score; 7 different questions/sensations (for each individual item 0-10 scale; 0= not present/no pain, 10= most sensation). Individual scores analyzed separately for pain quality and mean score analyzed for overall neuropathic pain).
Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8
To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in disability and function as measured by the Gait Speed Test
Time Frame: Baseline, Week 4, Week 8
Distance walked (meters)/time (seconds) measured by Gait Speed Test (lower score = worse, higher score =better)
Baseline, Week 4, Week 8
To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in mean changes in perceived improvement as measured by the Patient Global Impression of Change
Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8
Patient Global Impression of Change (PGIC) 1-7 point ordinal scale assessed (1 = worse, 7 = better)
Baseline, Week 2, Week 4, Week 6, Week 8
To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in mean changes in perceived improvement as measured by the patient satisfaction visual analog scale.
Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8
Patient satisfaction with intervention on visual analog scale (VAS, 0-100, 0=no satisfaction, 100 = complete satisfaction).
Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8
To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in mean changes in quality of life measured by the Veterans RAND 12 Item Health Survey
Time Frame: Baseline, Week 4, Week 8
Mental Component Score (MCS) and Physical Component Score (PCS) measured by Veterans RAND 12 Item Health Survey (VR-12). VR-12 is an algorithmic score with ranges from 0-100 (0 indicates worse health-related quality of life and 100 represents better health-related quality of life).
Baseline, Week 4, Week 8
To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in anxiety measured by the Generalized Anxiety Disorder-7.
Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8
Generalized anxiety symptomology is measured by Generalized Anxiety Disorder-7 (GAD-7) total score. (total score ranges from 0-21; Score 0-4 = minimal anxiety, Score 5-9 = mild anxiety, Score 10-14 = moderate anxiety, Score 15-21 = severe anxiety)
Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8
To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in pain quality as measured by the Short Form McGill Pain Questionnaire (SF-MPQ-2).
Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8
Short Form McGill Pain Questionnaire (SF-MPQ-2) total score and four subscales (continuous pain, intermittent pain, predominantly neuropathic pain, affective). (0= no pain to 5= excruciating pain)
Baseline, Week 2, Week 4, Week 6, Week 8
To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in mean changes in disability and function as measured by the Brief Pain Inventory-Diabetic Peripheral Neuropathy.
Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8
Brief Pain Inventory-Diabetic Peripheral Neuropathy (BPI-DPN) pain intensity score (first four items 0-10; 10= pain as bad as can imagine) (remaining items 0% (no relief)-100% (complete relief)) and pain interference score (0-10, 10= completely intense).
Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8
To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in emotional functioning (severity of depression) as measured by the Patient Health Questionnaire-9.
Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8
Severity of depression is measured by Patient Health Questionnaire-9 (PHQ-9) total score (0-27; 0=none, 27=worst).
Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8
To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in emotional functioning (PTSD symptoms) as measured by the PTSD Checklist-DSM-5 (PCL-5).
Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8
PTSD symptoms are assessed by PTSD Checklist-DSM-5 (PCL-5) total score symptom severity score (0-80; 0= not at all to 80= worst).
Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
VA Office of Research and Development

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Deepak D'Souza, MD MBBS, VA Connecticut Healthcare System West Haven Campus, West Haven, CT
  • Principal Investigator: Donald McGeary, PhD, South Texas Health Care System, San Antonio, TX

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 21, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 29, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 31, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 8, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 22, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 28, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 23, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NURP-002-20F

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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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