Table 5.
Experimental studies: effect of cannabinoids on spasticity.
| Author, Year |
Inclusion
Criteria |
Exclusion Criteria | Number of Participants (SCI/Total) |
Male/
Female |
Mean Age |
Tetraplegia/
Paraplegia |
Mean Time Since
Injury |
Inter-
vention |
Comparison | Spasticity Measures | Outcome | Effect Size | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Randomized Control Trials (Mixed Samples) | ||||||||||||||||||||||||
| *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) | NRS spasticity, AS, 10-point spasticity severity scale; spasm frequency/day | ↓ Spasticity (2wk NRS p<0.05) |
NRS spasm/d: ↓ 0.34 NRS spasticity/d: ↓ 0.29 Severity 2wk: ↓ 0.73 Frequency 2wk: ↓ 0.35 |
||||||||||||
| THC-rich sublingual spray (2.5mg–max 120mg/d) f/u: 2 wks |
Placebo (Inert Plant Material) | ↓ Spasticity (daily, 2wk NRS p<0.05) | NRS spasm/d: ↓ 0.48 NRS spasticity/d: ↓ 0.75 Severity 2wk: ↓ 0.73 Frequency 2wk: ↓ 0.95 |
|||||||||||||||||||||
| 1:1 THC:CBD sublingual spray (2.5mg–max 120mg/d) f/u: 2 wks |
Placebo (Inert Plant Material) | ↓ Spasticity (daily, 2wk NRA p<0.05) | NRS spasm/d: ↓ 0.35 NRS spasticity/d: ↓ 0.09 Severity 2wk: ↓ 0.62 Frequency 2wk: ↓ 0.89 |
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| *Hagenbach et al., 2007 [55] **RCT phase |
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 | 13/13 | 11/2 | 40.9y (29-66y) |
5/8 | 14.3y (3y-29y) |
Dronabinol capsule oral (2.5mg, 5.0mg, 10.0mg) f/u: 1, 8, 43d |
Placebo (sesame oil) | MAS, 7-point spasticity severity scale | ↓ Spasticity (p=0.001 placebo of this phase vs open label of oral phase) (day one self-rating p=0.033) | MAS: ↓ 0.61 | ||||||||||||
| **Non-RCT phase | 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 | ↓ Spasticity (AS at 1/8d p<0.001, 43d p<0.05) |
- | |||||||||||||||
| 8/8 | 8/0 | 48.8y (32-66y) | 5/3 | 15.5y (5-28y) |
Rectal THC (5.0mg, 10.0mg) f/u: 1, 8, 43d |
Baseline | ↓ Spasticity (AS at 1/8/43d p<0.05) | - | ||||||||||||||||
| *Pooyania et al., 2010 [77] | Aged 18-65 with a level of injury at C5 or below, and injury occurred more than 1 year previously. Stable neurologic level, with moderate spasticity (>3 AS). Spasticity medications had to be unchanged for at least 30 days before inclusion and no botulinum toxin injections >4 months |
History of heart disease, psychotic disorders, schizophrenia, or any active psychologic disorder. Previously documented sensitivity to marijuana or other cannabinoid agents, severe liver dysfunction, cognitive impairment, a major illness in another body area, fixed tendon contractures. Pregnant or nursing. History of drug dependency, smoked cannabis <30d before study onset, or unwilling to not smoke during the study | 12/12 | 12/0 | 42.4y | 6/6 | NR | Nabilone (0.5mg-1.0mg/d) f/u: 4wks |
Placebo | AS, Spasm frequency scale, VAS spasticity, Pendulum test, Global Impression of Change (subject/ clinician) |
↓ Spasticity (aAS in most spasticity group p=0.003, AS in 8 muscle groups p=0.001) | 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 | Spasticity Measures | Outcome | Effect Size | ||||||||||||
| Randomized Control Trials (Mixed Samples) | ||||||||||||||||||||||||
| *Wilsey et al., 2016 [60] |
Age 18-70, 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 | 11-point spasticity severity scale (spasms, pain, muscle stiffness), Global Impression of Change | ↓ Spasticity (420min p<0.0001) ↑ Relief (p=0.0227) |
Insufficient data | ||||||||||||
| 6.7% delta 9-THC vaporized cannabis (4-8 puffs) f/u: 60, 120, 180, 240, 300, 360, 420min |
Placebo | = Spasticity | Insufficient data | |||||||||||||||||||||
| Pre-/Post-Studies (SCI samples) | ||||||||||||||||||||||||
| *Kogel et al., 1995 [76] |
SCI staff selected. Chronic problematic spasticity that has not responded to more commonly prescribed spasmolytic medications. | - | 5/5 | 5/0 | 41y (28-55y) |
5/0 | 6mo-9y | Dronabinol (15.0 mg – 60.0mg/d) f/u: 5d |
Baseline | Pendulum Drop Test | ↓ Spasticity | |||||||||||||
Note: a:clinically meaningful change in AS as defined as a decrease of 1 point. ↑: increase; ↓: decrease; =: no change; *: pain studied as a primary outcome; AS: Ashworth Scale; CBD: cannabidiol; d: day; f/u: follow-up; MAS: Modified Ashworth Scale; mo: month; NR: not reported; NRS: numerical rating scale; SCI: spinal cord injury; THC: tetrahydrocannabinol; UC: University California; wks: weeks, y: years.