Effects of Vaporized Marijuana on Neuropathic Pain

• Sponsor: University of California, Davis (Other)
• Overall Status: Completed
• CT.gov ID: NCT01037088
• Collaborator: Center for Medicinal Cannabis Research (Other), VA Northern California Health Care System (U.S. Fed)
• Enrollment: 44
• Location: 1
• Arms: 3
• Duration (Months): 35
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

This study theorized that a low dose of vaporized cannabis could alleviate nerve injury pain.

Condition or Disease	Intervention/Treatment	Phase
Neuropathic Pain; Reflex Sympathetic Dystrophy; Peripheral Neuropathy; Post-herpetic Neuralgia; Spinal Cord Injury; Multiple Sclerosis	Drug: Mild dose cannabis; Drug: Low dose cannabis; Drug: Cannabis	Phase 1/Phase 2

Detailed Description

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: CCRC: The Analgesic Effect of Vaporized Cannabis on Neuropathic Pain
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mild dose cannabis 3.53% THC by weight	Drug: Mild dose cannabis; 3.53% THC by weight; Other Names: marijuana
Experimental: Low dose cannabis 1.29% THC by weight	Drug: Low dose cannabis; 1.29% THC by weight; Other Names: marijuana
Placebo Comparator: Placebo cannabis placebo marijuana	Drug: Cannabis; 0.00% THC by weight; Other Names: placebo marijuana

Outcome Measures

Primary Outcome Measures

1. Participants With 30% or Greater Reduction in Pain Intensity [baseline to six hours]

   The primary outcome variable, VAS Pain Intensity, was assessed by asking participants to indicate the intensity of their current pain on a 100-mm visual analog scale (VAS) between 0 (no pain) and 100 (worst possible pain).An assessment was performed before the administration of vaporized cannabis or placebo and hourly thereafter for six hours.

Secondary Outcome Measures

1. Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis [baseline to six hours]

   The pain intensity scores for all of the time points (i.e., baseline prior to administration and up to 5 hours following administration of cannabis). VAS Pain Intensity was assessed by asking participants to indicate the intensity of their current pain on a 100-mm visual analog scale (VAS) between 0 (no pain) and 100 (worst possible pain).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age greater than 18 and less than 70

• Visual Analogue Scale (VAS pain intensity) greater than 3/10

• A negative urine drug screening test, i.e., no evidence of IV drug abuse

• Neuropathic pain due to reflex sympathetic dystrophy, peripheral neuropathy, post-herpetic neuralgia, post-stroke pain, multiple sclerosis or spinal cord injury

Exclusion Criteria:

• Presence of another painful condition of greater severity than the neuropathic pain condition which is being studied.

• Subjects with moderate-severe major depression, bipolar/mania, bipolar II/hypomania and schizophrenia or schizoaffective disorder.

• Unstable Type 1 or 2 diabetes defined as blood glucose more than 156 mg/dl

• History of traumatic brain injury

• Uncontrolled medical condition, including coronary artery disease, hypertension, cerebrovascular disease, asthma, tuberculosis (TB), chronic obstructive pulmonary disease (COPD), opportunistic infection, malignancy requiring active treatment, active substance abuse (alcohol or injection drugs).

• Current use of marijuana (e.g., within 30 days of randomization)

• Pregnancy as ascertained by a self-report and a mandatory commercial pregnancy test.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CTSC Clinical Research Center, Sacramento VA Medical Center	Sacramento	California	United States	95817

Sponsors and Collaborators

• University of California, Davis
• Center for Medicinal Cannabis Research
• VA Northern California Health Care System

Investigators

• Principal Investigator: Barth L Wilsey, MD, University of California, Davis

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Center for Medicinal Cannabis Research website

Publications

• Wilsey B, Marcotte T, Tsodikov A, Millman J, Bentley H, Gouaux B, Fishman S. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain. 2008 Jun;9(6):506-21. doi: 10.1016/j.jpain.2007.12.010. Epub 2008 Apr 10.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT01037088
• Other Study ID Numbers: 200614658; C06-DA-119
• First Posted: Dec 21, 2009
• Last Update Posted: Jan 31, 2018
• Last Verified: Oct 1, 2017

• Keywords provided by University of California, Davis: cannabis; marijuana; neuropathy; antinociception; mood; cognition; neuropathic pain
• Additional relevant MeSH terms: Multiple Sclerosis; Spinal Cord Injuries; Neuralgia; Peripheral Nervous System Diseases; Neuralgia, Postherpetic; Reflex Sympathetic Dystrophy; Complex Regional Pain Syndromes

Study Results

Participant Flow

Recruitment Details	Recruitment took place at the UCDMC and VA Northern California Pain clinics,UCDMC Spinal Cord Injury Clinic, and newspaper advertisements. Between December 2009 and March 2011, 59 patients were consented to enroll in the study.
Pre-assignment Detail	Twenty subjects did not receive study medication: 9 withdrew for various reasons and 11 were disqualified following a medical evaluation with subsequent disclosure of exclusionary criteria on a physical exam or laboratory finding.

Arm/Group Title	All Participants
Arm/Group Description	All participants were randomized to a 3 way cross over design and received 3.53% THC, 1.29% THC and placebo cannabis.
Period Title: Overall Study
STARTED	39
Received 3.53% THC	36
Received 1.29% THC	37
Received Placebo	38
COMPLETED	36
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	All participants who were randomized
Overall Participants	39
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	39 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50 (11)
Sex: Female, Male (Count of Participants)
Female	11 28.2%
Male	28 71.8%
Region of Enrollment (participants) [Number]
United States	39 100%

Outcome Measures

1. Primary Outcome

Title	Participants With 30% or Greater Reduction in Pain Intensity
Description	The primary outcome variable, VAS Pain Intensity, was assessed by asking participants to indicate the intensity of their current pain on a 100-mm visual analog scale (VAS) between 0 (no pain) and 100 (worst possible pain).An assessment was performed before the administration of vaporized cannabis or placebo and hourly thereafter for six hours.
Time Frame	baseline to six hours

Outcome Measure Data

Analysis Population Description

This was a cross over study. Ten of the 38 subjects who were exposed to placebo had a 30% reduction in pain intensity as compared to 21 of the 37 exposed to the low dose and 22 of the 36 receiving the medium dose of cannabis.

Arm/Group Title	Mild Dose Cannabis	Low Dose Cannabis	Placebo Cannabis
Arm/Group Description	3.53% THC by weight	1.29% THC by weight	trace THC by weight
Measure Participants	36	37	38
Number (95% Confidence Interval) [percentage of participants]	61 156.4%	57 NaN	26 NaN

2. Secondary Outcome

Title	Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis
Description	The pain intensity scores for all of the time points (i.e., baseline prior to administration and up to 5 hours following administration of cannabis). VAS Pain Intensity was assessed by asking participants to indicate the intensity of their current pain on a 100-mm visual analog scale (VAS) between 0 (no pain) and 100 (worst possible pain).
Time Frame	baseline to six hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mild Dose Cannabis	Low Dose Cannabis	Placebo Cannabis
Arm/Group Description	3.53% THC by weight	1.29% THC by weight	0.00% THC by weight
Measure Participants	36	37	38
Baseline prior to Administration of Cannabis	57.3 (24.1)	54.4 (23.4)	57.5 (22.8)
Hour 1 after Administration of Cannabis	51.8 (22.1)	49.8 (25.7)	56.5 (24.1)
Hour 2 after Administration of Cannabis	44.3 (26.8)	45.8 (26.4)	55.4 (25.1)
Hour 3 after Administration of Cannabis	39.7 (25.8)	38.2 (27.1)	50.7 (25.0)
Hour 4 after Administration of Cannabis	40.4 (26.9)	39.5 (27.2)	48.1 (25.6)
Hour 5 after Administration of Cannabis	41.7 (25.5)	40.7 (27.2)	51.8 (25.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mild Dose Cannabis, Low Dose Cannabis, Placebo Cannabis
	Comments	Hour 1 after Administration of Cannabis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>.05
	Comments	not significant
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mild Dose Cannabis, Low Dose Cannabis, Placebo Cannabis
	Comments	Hour 2 after Administration of Cannabis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=.0002
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mild Dose Cannabis, Low Dose Cannabis, Placebo Cannabis
	Comments	Hour 3 after Administration of Cannabis (after the second inhalation of cannabis)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mild Dose Cannabis, Low Dose Cannabis, Placebo Cannabis
	Comments	Hour 4 after Administration of Cannabis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=.0004
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Mild Dose Cannabis, Low Dose Cannabis, Placebo Cannabis
	Comments	Hour 5 after Administration of Cannabis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=.0018
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Arm/Group Title	Mild Dose Cannabis		Low Dose Cannabis		Placebo Cannabis
Arm/Group Description	3.53% 9-delta tetrahydrocannabinol by weight		1.29% 9-delta tetrahydrocannabinol by weight		0% 9-delta tetrahydrocannabinol by weight
All Cause Mortality
	Mild Dose Cannabis		Low Dose Cannabis		Placebo Cannabis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Mild Dose Cannabis		Low Dose Cannabis		Placebo Cannabis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/37 (0%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	Mild Dose Cannabis		Low Dose Cannabis		Placebo Cannabis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/37 (0%)		0/38 (0%)

Limitations/Caveats

Inclusion of patients with complex regional pain syndrome type I. In the past, there was no doubt that this disorder should be classified as classical neuropathic pain condition; Unmasking of blinding secondary to the psychoactive effects of cannabis

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.