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NCT Number: NCT05351801

Proof of Concept Trial of Cannabis Derivatives in Neuropathic Pain

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.

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Key information

Conditions

Neuropathic Pain Nervous System Diseases Neuralgia Neurologic Manifestations Neuromuscular Diseases Pain Pathological Conditions, Signs and Symptoms Peripheral Nervous System Diseases Peripheral Neuropathic Pain Signs and Symptoms

Age range

21 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

VA San Diego Healthcare System, San Diego, CA, San Diego, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

THC (Syndros)

Drug

Participants will receive a target dose of 10mg per day of THC (Syndros).

CBD (Epidolex)

Drug

Participants will receive a target dose of 800 mg per day of CBD (Epidolex).

THC + CBD (Nabiximols)

Drug

Participants will receive a target dose of 10.8 mg / 10 mg per day of THC + CBD (Nabiximols).

Placebo

Drug

Placebo

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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)

  2. 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).

  3. 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)

  4. 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)

  5. 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).

  6. 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).

  7. 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)

  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)

  9. 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).

  10. 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).

  11. 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).

Study contacts

Contact information is provided by the study sponsor or research team.

Courtney C DiCocco

CONTACT

[email protected]

(203) 932-5711

Mohini Ranganathan, MD

CONTACT

[email protected]

(203) 932-5711

Sponsors and collaborators

Lead sponsor

VA Office of Research and Development

Fed

Registry information

Acronym: CAN

Important dates

Study start
2023
Primary completion
2028
Study completion
2029
First posted
Apr 28, 2022
Registry last updated
Feb 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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