Safety and Efficacy of Oral Cannabis in Chronic Spine Pain

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Safety and Efficacy of Oral Cannabis in Chronic Spine Pain

Conditions
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Back Pain, Neck Pain

Intervention / Treatment
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* Drug: THC/CBD
* Drug: THC
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 84 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: One Main Arm is Crossover (Analgesia Arm) One Main Arm is Parallel (Reduction Arm)
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Analgesia Arm: THC (tetrahydrocannabinol), then THC/CBD (cannabidiol), then Placebo<br>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<br>* Oral solution containing 5mg THC and 50 mg CBD per 1 ml<br>Drug: THC<br>* Oral solution containing 5mg THC per 1 ml<br>Drug: Placebo<br>* Oral solution containing no active drug<br>|
| Experimental: Analgesia Arm: THC, then Placebo, then THC/CBD<br>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<br>* Oral solution containing 5mg THC and 50 mg CBD per 1 ml<br>Drug: THC<br>* Oral solution containing 5mg THC per 1 ml<br>Drug: Placebo<br>* Oral solution containing no active drug<br>|
| Experimental: Analgesia Arm: THC/CBD, then THC, then Placebo<br>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<br>* Oral solution containing 5mg THC and 50 mg CBD per 1 ml<br>Drug: THC<br>* Oral solution containing 5mg THC per 1 ml<br>Drug: Placebo<br>* Oral solution containing no active drug<br>|
| Experimental: Analgesia Arm: THC/CBD, then Placebo, then THC<br>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<br>* Oral solution containing 5mg THC and 50 mg CBD per 1 ml<br>Drug: THC<br>* Oral solution containing 5mg THC per 1 ml<br>Drug: Placebo<br>* Oral solution containing no active drug<br>|
| Experimental: Analgesia Arm: Placebo, then THC, then THC/CBD<br>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<br>* Oral solution containing 5mg THC and 50 mg CBD per 1 ml<br>Drug: THC<br>* Oral solution containing 5mg THC per 1 ml<br>Drug: Placebo<br>* Oral solution containing no active drug<br>|
| Experimental: Analgesia Arm: Placebo, then THC/CBD, then THC<br>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<br>* Oral solution containing 5mg THC and 50 mg CBD per 1 ml<br>Drug: THC<br>* Oral solution containing 5mg THC per 1 ml<br>Drug: Placebo<br>* Oral solution containing no active drug<br>|
| Experimental: Reduction Arm: THC/CBD<br>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<br>* Oral solution containing 5mg THC and 50 mg CBD per 1 ml<br>|
| Placebo Comparator: Reduction Arm: Placebo<br>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<br>* Oral solution containing no active drug<br>|

What is the study measuring?
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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 3x3 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) |