Table 3.
Experimental studies: effect of cannabinoids on pain.
| Author, Year | Inclusion Criteria | Exclusion Criteria | Number of Participants (SCI/Total) |
Male/
Female |
Mean Age |
Tetraplegia/
Paraplegia |
Mean Time Since Injury | Intervention | Comparison | Pain Measures | Outcome | Effect Size | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Randomized Control Trials (Mixed Samples) | ||||||||||||||||||||||||
| *Karst et al., 2003 [56] |
Neuropathic and somatic pain for >6mo, stable levels of pain medications for >2mo. Aged 18-65y. Consent to participate in study and follow study procedures | No N-methyl-D-aspartate receptor antagonist and cannabinoid concomitant pain-relieving medications. Severe organic or psychiatric disease, pregnancy/attempting to conceive, lactation, use of any investigational drug within 30d prior to the first dose of study drug, non-German speaking | 3/21 | 13/8 | 51y (21-65y) |
0/3 | NR | CT-3 (10.0mg–max 80.0mg) before placebo sequence f/u: 3, 8 hrs |
Placebo | VRS pain, VAS pain (100-mm scale) | ↓ Pain (3hrs: VAS p=0.02, VRS p=0.10) 8hrs: VAS p=0.21, VRS p=0.14) |
3hr VRS: ↓0.55/↓0.50 3hr VAS: ↓0.82/↓0.52 8hr VRS: ↓0.39/↓0.54 8hr VAS: ↓0.52/↓0.17 |
||||||||||||
| *Wade et al., 2003[58] |
Neurologic diagnosis and be able to identify troublesome symptoms which were stable and unresponsive to standard treatments. | History of drug or alcohol abuse, serious psychiatric illness (excluding depression associated with neurological condition), serious cardiovascular disease or active epilepsy | 4/20 | 10/10 | 48y | NR | NR | CBD-rich sublingual spray (2.5mg–max 120mg/d) f/u: 2 wks |
Placebo (Inert Plant Material) | VAS pain (daily 100-mm scale, 2wk 11-point scale) | ↓ Pain (daily VAS p<0.05) |
VAS pain/d: ↓0.45 VAS pain 2wk: ↓0.19 |
||||||||||||
| THC-rich sublingual spray (2.5mg–max 120mg/d) f/u: 2 wks |
Placebo (Inert Plant Material) | ↓ Pain (daily VAS p<0.05) |
VAS pain/d: ↓0.39 VAS pain 2wk: ↓0.82 |
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| 1:1 THC:CBD sublingual spray (2.5mg–max 120mg/d) f/u: 2 wks |
Placebo (Inert Plant Material) | = Pain | VAS pain/d: ↓0.19 VAS pain 2wk: ↓0.16 |
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| *Wilsey et al., 2008 [59] |
Adults with complex regional pain syndrome (CRPS type 1), SCI, peripheral neuropathy, or nerve injury. Previous cannabis exposure. Must refrain from smoking cannabis or taking oral synthetic delta-9-THC medications for 30d before study session | Candidates who met the criteria for severe major depressive disorder, or candidates with a history or diagnosis of schizophrenia or bipolar depression. Uncontrolled hypertension, cardiovascular disease, chronic pulmonary disease (asthma, chronic pulmonary obstructive disease), active substance abuse | 6/38 | 20/18 | 46y (21-71y) |
NR | 6y (10mo-24y) |
3.5% delta 9-THC cigarettes (9 puffs) f/u: 1, 2, 3, 4, 5, 6 hrs |
Placebo | VAS pain intensity (100-mm scale), VAS pain unpleasantness, Global Impression of Change, Neuropathic pain scale, VAS allodynia, Heat pain threshold | ↓ Pain (p=0.03 CI -0.0069 to -0.0003) ↓ Pain Unpleasantness (p<0.01 CI -0.33 to -0.09) ↑ Global Impression of Change of Pain (p<0.01 CI 0.064 to 0.018) ↓ Neuropathic Pain Scale (sharp, burning, aching, deep pain p<0.001; superficial p<0.04; sensitive p<0.03) |
Insufficient data | ||||||||||||
| 7% delta 9-THC cigarettes (9 puffs) f/u: 1, 2, 3, 4, 5, 6 hrs |
Placebo | ↓ Pain (p=0.04 CI -0.0068 to -0.0002) ↓ Pain Unpleasantness (p<0.01 CI -0.33 to -0.09) ↑ Global Impression of Change of Pain (p<0.01 CI 0.065 to 0.018) ↓ Neuropathic Pain Scale (sharp, burning, aching, deep pain p<0.001; superficial p<0.01; sensitive p<0.03) |
Insufficient data | |||||||||||||||||||||
| Author, Year | Inclusion Criteria | Exclusion Criteria | Number of Participants (SCI/Total) |
Male/ Female |
Mean Age |
Tetraplegia/ Paraplegia |
Mean Time Since Injury | Intervention | Comparison | Pain Measures | Outcome | Effect Size | ||||||||||||
| Randomized Control Trials (Mixed Samples) | ||||||||||||||||||||||||
| *Rintala et al., 2010 [57] |
Adults who had sustained an SCI >12 before study entry and who reported chronic (>6 mo) neuropathic pain, the intensity of which was rated as >5 at its worst on a scale of 0-10 | Previous adverse reaction to any cannabinoid or sesame oil, current or history substance abuse, serious psychological or psychiatric disorder, renal or hepatic insufficiency, history of tachycardia, pregnant or nursing | 7/7 | 5/2 | 50.1 ± 8.3y | ¾ | 21.9 ± 9.3y (4-32y) | Dronabinol (5.0mg–max 20.0mg) f/u: 2, 4 wks |
Placebo (diphenhydramine) | Brief Pain Inventory | = Pain | Brief Pain Inventory: ↑0.83 | ||||||||||||
| *Wilsey et al., 2016 [60] |
Age 18-70y, with pain intensity >4/10, who attend the UC Davis Medical Center Spinal Cord Injury Clinic | Diagnosis of bipolar depression, schizophrenia, severe depression, or affirmation to the statements “I felt life was not worth living”; “I felt like hurting myself”; “I felt like killing myself”. A history of coronary artery disease, obstructive pulmonary disease, severe liver disease, impaired renal function. Current substance use disorder. |
29/42 | 29/13 | 46.4y | NR | 11.6 ± 10.1y | 2.9% delta 9-THC vaporized cannabis (4-8 puffs) f/u: 60, 120, 180, 240, 300, 360, 420min |
Placebo | VAS 100-mm pain scale, Patient Global Impression of Change, Neuropathic Pain Scale, VAS allodynia, Heat-pain threshold | ↓ Pain Intensity (60min p<0.05, 120/240min p<0.01, 300min p<0.05, 360min p<0.05, 420min p<0.05) ↑ Pain Relief (60, 120, 240, 300, 420min p<0.0001) *given second dose at 240min ↓ all neuropathic pain except itching (p<0.0001) |
Insufficient data | ||||||||||||
| 6.7% delta 9-THC vaporized cannabis (4-8 puffs) f/u: 60, 120, 180, 240, 300, 360, 420min |
Placebo | ↓ Pain Intensity (60min p<0.05, 300min p<0.05, 360min p<0.05, 420min p<0.05) ↑ Pain Relief (60, 120, 240, 300, 360min p<0.0001) *given second dose at 240min ↓ all neuropathic pain except itching (p<0.0001) |
Insufficient data | |||||||||||||||||||||
| Pre-/Post-Studies (SCI samples) | ||||||||||||||||||||||||
| Hagenbach et al., 2007 [55] Open-label |
Terminated taking all spasmolytic medication >3 half-life periods before enrolling, free of illegal drugs. Spasticity without any spasmolytic treatment had to be >3points on the MAS in at least one muscle group | Pregnant, severe somatic and known psychiatric diseases | 22/22 | 20/2 | 40.9y (19-73y) | 11/11 | 13.3y (2-29y) |
Dronabinol capsule oral (2.5mg, 5.0mg, 10.0mg) f/u: 1, 8, 43d |
Baseline | 6-point pain scale | ↓ Pain (1d p=0.047) | |||||||||||||
Abbreviations: ↑: increase; ↓: decrease; =: no change; *: pain studied as a primary outcome; CBD: cannabidiol; CT-3: 1’,1’-dimethylheptyl-Δ8-tetrahydrocannabinol-11-oic acid in capsules; CI: confidence interval; d: day; f/u: follow-up; MAS: Modified Ashworth Scale; mo: month; NR: not reported; SCI: spinal cord injury; THC: tetrahydrocannabinol; UC: University of California; VAS: visual analog scale; VRS: verbal rating scale; wks: weeks, y: years.