Safety and Efficacy of Oral Cannabis in Chronic Spine Pain

The overall objectives of this study are to investigate the efficacy of extended cannabis treatment to reduce patient exposure to prescription opioids through its use 1) as a non-opioid analgesic treatment, and 2) as a therapy for reducing high-dose opioid use in patients with chronic spine pain.

Study Overview

• Status: Not yet recruiting
• Conditions: Back Pain; Neck Pain
• Intervention / Treatment: Drug: THC/CBD; Drug: THC; Drug: Placebo

Detailed Description

This randomized, placebo-controlled clinical trial is designed to elucidate the role of extended oral cannabis treatment in the alleviation of chronic spine pain and reduction of high-dose opioid use. This trial includes two study arms: Analgesia Arm and Reduction Arm. The Analgesia Arm uses a within-subject crossover design to determine whether daily treatment with an oral cannabis solution for 6 weeks significantly reduces spine pain compared to placebo. The Reduction Arm uses a parallel design to determine whether daily treatment with an oral cannabis solution for 13 weeks results in a greater reduction of pain and opioid intake than placebo treatment. It will also assess the impact of extended cannabis treatment on opioid craving and symptoms of opioid withdrawal in participants tapering their high-dose opioids.

• Study Type: Interventional
• Enrollment (Anticipated): 157
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Alan Morris, PhD; Phone Number: 303-724-0923; Email: CUPainStudies@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus
      • Contact: Emily Lindley, PhD; Phone Number: 303-724-0239; Email: emily.lindley@cuanschutz.edu
      • Principal Investigator: Rachael Rzasa Lynn, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 84 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Some inclusion/exclusion criteria are purposely omitted at this time to preserve scientific integrity. They will be included after the trial is complete.

Inclusion Criteria:

Documented chronic (≥3 months' duration), non-radicular spine pain

Exclusion Criteria:

Unwilling/unable to refrain from cannabis use (medical or recreational) for 14 days prior to Baseline Visit and throughout the study (other than study drug). This includes whole plant inhalation, edibles, extracts, and topicals.

Co-morbid cancer-related pain condition

Neuropathic Pain

A co-morbid pain condition that is of greater severity than the patient's spine pain

Spine or other major surgery within the 3 months prior to enrollment

Planned surgery or procedural intervention during the study period

Allergy or adverse reaction to cannabis

Current or historical substance use disorder

Current or historical alcohol use disorder

Current or prior cannabis abuse/dependence

Positive result for use of amphetamine/methamphetamine, barbiturates, benzodiazepines, cocaine, phencyclidine (PCP), ecstasy (MDMA), as detected on urine screen

Current use of valproate, clobazam, clopidogrel, warfarin, barbiturates, benzodiazepines

Prior adverse reaction to cannabis exposure (paranoia, anxiety, etc.)

History or diagnosis of schizophrenia, bipolar or a psychotic disorder

History of any mental health illness that in the opinion of the Investigator would compromise the safety of the participant

Current or historical severe depression

Current suicidal ideation

Diagnosed cognitive impairment (e.g. Alzheimer's Disease, traumatic brain injury)

Uncontrolled hypertension (>139/89)

Abnormal values on CBC (complete blood count) or CMP (comprehensive metabolic panel) laboratory analysis that are deemed clinically significant by study physician

Known hepatic disease or dysfunction, or identification of such on screening laboratory studies

Known cardiovascular disease

Abnormal result on electrocardiogram (ECG) that is deemed clinically significant by study MD

Cognitive disability that interferes with ability to provide consent or understand study procedure

History of seizure disorder

Diagnosed autoimmune or rheumatological disease such as rheumatoid arthritis (RA) or multiple sclerosis (MS)

Inability to refrain from using tobacco for at least 4 hours

Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the participant or the quality of the data

Pending legal action or workers compensation

Pregnant females or females intending to become pregnant during the study period

Unwilling to use one of the accepted forms of contraception during the study period and for at least 60 days after completion of the study (females of childbearing potential and males with sexual partners of childbearing potential)

Lactating females

Analgesia Arm Exclusion Criteria:

Unwilling/unable to discontinue current opioid use for 14 days prior to Baseline study visit and throughout the study

Reduction Arm Exclusion Criteria:

Not interested in reducing or discontinuing use of prescribed opioids for chronic pain

Unwilling to allow the study team to communicate with the participant's opioid prescribing provider

*Some inclusion/exclusion criteria are purposely omitted at this time to preserve scientific integrity. They will be included after the trial is complete.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Analgesia Arm: THC (tetrahydrocannabinol), then THC/CBD (cannabidiol), then Placebo; Subjects in this crossover arm will be assigned to 6 weeks on THC oral solution, then 6 weeks on THC/CBD oral solution, then 6 weeks on Placebo oral solution. Frequency of drug administration is 3-4 times a day.	Drug: THC/CBD; Oral solution containing 5mg THC and 50 mg CBD per 1 ml; Drug: THC; Oral solution containing 5mg THC per 1 ml; Drug: Placebo; Oral solution containing no active drug
Experimental: Analgesia Arm: THC, then Placebo, then THC/CBD; Subjects in this crossover arm will be assigned to 6 weeks on THC oral solution, then 6 weeks on Placebo oral solution, then 6 weeks on THC/CBD oral solution. Frequency of drug administration is 3-4 times a day.	Drug: THC/CBD; Oral solution containing 5mg THC and 50 mg CBD per 1 ml; Drug: THC; Oral solution containing 5mg THC per 1 ml; Drug: Placebo; Oral solution containing no active drug
Experimental: Analgesia Arm: THC/CBD, then THC, then Placebo; Subjects in this crossover arm will be assigned to 6 weeks on THC/CBD oral solution, then 6 weeks on THC oral solution, then 6 weeks on Placebo oral solution. Frequency of drug administration is 3-4 times a day.	Drug: THC/CBD; Oral solution containing 5mg THC and 50 mg CBD per 1 ml; Drug: THC; Oral solution containing 5mg THC per 1 ml; Drug: Placebo; Oral solution containing no active drug
Experimental: Analgesia Arm: THC/CBD, then Placebo, then THC; Subjects in this crossover arm will be assigned to 6 weeks on THC/CBD oral solution, then 6 weeks on Placebo oral solution, then 6 weeks on THC oral solution. Frequency of drug administration is 3-4 times a day.	Drug: THC/CBD; Oral solution containing 5mg THC and 50 mg CBD per 1 ml; Drug: THC; Oral solution containing 5mg THC per 1 ml; Drug: Placebo; Oral solution containing no active drug
Experimental: Analgesia Arm: Placebo, then THC, then THC/CBD; Subjects in this crossover arm will be assigned to 6 weeks on Placebo oral solution, then 6 weeks on THC oral solution, then 6 weeks on THC/CBD oral solution. Frequency of drug administration is 3-4 times a day.	Drug: THC/CBD; Oral solution containing 5mg THC and 50 mg CBD per 1 ml; Drug: THC; Oral solution containing 5mg THC per 1 ml; Drug: Placebo; Oral solution containing no active drug
Experimental: Analgesia Arm: Placebo, then THC/CBD, then THC; Subjects in this crossover arm will be assigned to 6 weeks on Placebo oral solution, then 6 weeks on THC/CBD oral solution, then 6 weeks on THC oral solution. Frequency of drug administration is 3-4 times a day.	Drug: THC/CBD; Oral solution containing 5mg THC and 50 mg CBD per 1 ml; Drug: THC; Oral solution containing 5mg THC per 1 ml; Drug: Placebo; Oral solution containing no active drug
Experimental: Reduction Arm: THC/CBD; Subjects in this parallel arm will be assigned to 13 weeks on THC/CBD oral solution. Frequency of drug administration is 3-4 times a day.	Drug: THC/CBD; Oral solution containing 5mg THC and 50 mg CBD per 1 ml
Placebo Comparator: Reduction Arm: Placebo; Subjects in this parallel arm will be assigned to 13 weeks on Placebo oral solution. Frequency of drug administration is 3-4 times a day.	Drug: Placebo; Oral solution containing no active drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in chronic pain as measured by the Visual Analog Scale (VAS) for pain	The Visual Analog Scale (VAS) for pain is a 0-100mm visual scale anchored by "no pain" and "worst possible pain".	Weekly, up to week 22
Change in opioid dose as measured in morphine milligram equivalents (MME)		Weekly, up to week 22

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study Drug Tolerability as measured by study drug use	study drug dose, frequency	Daily, up to week 22
Study Drug Tolerability as measured by side effects		Daily, up to week 22
Change in spine-related disability and quality of life as measured on the NIH Patient Reported Outcomes Measurement System (PROMIS)-29	The NIH Patient Reported Outcomes Measurement System (PROMIS)-29 is a collection of 4-item short forms assessing anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, and ability to participate in social roles and activities as well as a single pain intensity item.	Weekly, up to week 22
Change in spine-related disability and quality of life as measured on the NIH Task Force on Research Standards for Chronic Low-Back/Neck Pain Minimal Dataset	The NIH Task Force on Research Standards for Chronic Low-Back Pain Minimal Dataset (and the modified Dataset for neck pain) assesses the influence of back/neck pain on physical function, emotional health, sleep, everyday activities.	Weekly, up to week 22
Change in use of opioid and non-opioid analgesic medications		Daily, up to week 22
Change in abuse liability of cannabis as measured on the Drug Effects Questionnaire (DEQ) for study drug (cannabis)	The Drug Effects Questionnaire (DEQ) for study drug (cannabis) assesses the subjective effects after taking a drugs, including feeling a drug effect, liking/disliking the drug effect, feeling high, and wanting more drug.	Weekly, up to week 22
Change in abuse liability of cannabis as measured on a VAS for study drug (cannabis) craving	The VAS for study drug (cannabis) craving is a 100 mm visual scale anchored by "not at all" and "extremely" when asked about drug craving in the past week	Weekly, up to week 22
Change in opioid craving and withdrawal as measured on a VAS for opioid craving	The VAS for opioid craving is a 100 mm visual scale anchored by "not at all" and "extremely" when asked about opioid craving in the past week.	Weekly, up to week 22
Change in opioid craving and withdrawal as measured on the Subjective Opiate Withdrawal Scale (SOWS)	The Subjective Opiate Withdrawal Scale (SOWS) is a self-report questionnaire containing 16 symptoms related to opioid withdrawal.	Weekly, up to week 22
Change in opioid craving and withdrawal as measured on the Drug Effect Questionnaire (DEQ)	The Drug Effects Questionnaire (DEQ) for opioids assesses the subjective effects after taking opioids, including feeling a drug effect, liking/disliking the drug effect, feeling high, and wanting more opioids.	Weekly, up to week 22
Change in opioid craving and withdrawal as measured on the Current Opioid Misuse Measure (COMM).	Current Opioid Misuse Measure (COMM) is a brief patient self-assessment to help identify participants who exhibit aberrant behaviors associated with the misuse of opioid medications.	Weekly, up to week 22
Change in pain sensitivity as measured by pain threshold (kPa) to a pressure stimulus	Pressure output on a computer-controlled pressure algometer will be set to 10 kPa/s and participants will be instructed to indicate when the sensation changes from one of pressure alone to one of pressure and pain (pain threshold) by pressing a button on the remote-control indicator	Weekly, up to week 22
Change in cognition as assessed by the List Sorting Working Memory Test	The List Sorting Working Memory Test measures attention/working memory. Participants recall and sequence different visually and orally presented stimuli (e.g., participants are asked to list a set of given animals in order by size, from smallest to largest).	Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
Change in cognition as assessed by the Pattern Comparison Processing Speed Test	The Pattern Comparison Processing Speed Test is a measure of processing speed. Participants discern whether two side-by-side pictures are the same or not, with 85 seconds to respond to as many items as possible.	Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
Change in cognition as assessed by the Oral Symbol Digit Test	The Oral Symbol Digit Test is a measure of processing speed. Symbols on the screen are associated with a number in a key. Participants are then presented symbols without numbers. Participants say each number that goes with each presented symbol for 90 seconds.	Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
Change in cognition as assessed by the Flanker Inhibitory Control and Attention Test	The Flanker Inhibitory Control and Attention Test measures attention and inhibitory control. Participants are required to indicate the left-right orientation of a centrally presented stimulus while inhibiting attention to the potentially incongruent stimuli that surround it (i.e., the flankers, two on either side).	Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
Change in cognition as assessed by the Picture Vocabulary Test	The Picture Vocabulary Test measures receptive vocabulary. Respondents select pictures (from arrays) that most closely match the meanings of presented words.	Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
Change in cognition and motor skills as assessed by the Hopkins Verbal Learning Test Revised (HVLT-R)	The HVLT-R is a measure of verbal learning and memory. Participants are asked to learn a 12-item word list over three trials (total immediate learning). A delayed free recall trial is administered after 20 minutes, followed by a yes/no recognition trial.	Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
Change in motor skills as assessed by the Grooved Pegboard Test	The Grooved Pegboard is a test of fine motor coordination and speed. In this test, participants place 25 small metal pegs into holes on a 3"x3" metal board as quickly as possible. All pegs are alike and have a ridge on 1 side that corresponds to a randomly oriented notch in each hole on the metal board.	Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
Change in motor skills as assessed by the Standardized Field Sobriety Test	The Standardized Field Sobriety Test is intended to detect driving impairments due to recent alcohol or drug use.	Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
Change in participant's perceived improvement in spine pain as measured on the Patient Global Impression of Change Scale (PGIC)	The Patient Global Impression of Change Scale (PGIC) is a 7-point scale depicting a patient's rating of overall improvement.	Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 2-arachidonoylglycerol levels as measured in plasma	2-arachidonoylglycerol will be measured in pmol/ml	Baseline, Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
Change in N-arachidonoylethanolamine levels as measured in plasma	N-arachidonoylethanolamine will be measured in pmol/ml	Baseline, Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
Change in tumor necrosis factor alpha (TNF-α) levels as measured in plasma	TNF-α will be measured in pg/ml	Baseline, Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
Change in C-reactive protein (CRP) levels as measured in plasma	CRP will be measured in mg/L	Baseline, Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Colorado Department of Public Health and Environment
• Investigators: Principal Investigator: Emily Lindley, PhD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2023
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: August 18, 2021
• First Submitted That Met QC Criteria: September 13, 2021
• First Posted (Actual): September 22, 2021

Study Record Updates

• Last Update Posted (Estimate): January 10, 2023
• Last Update Submitted That Met QC Criteria: January 6, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Neck Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol
• Other Study ID Numbers: 20-0701

Drug and device information, study documents

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