Table 2.
Principal characteristics of clinical studies reporting the use of Cannabis for neuropathic relief.
| Vaporized Administration | ||||||||
|---|---|---|---|---|---|---|---|---|
| Reference | Indication | Study Design and No. of Patients (pts). | Period of Treatment | Dose | Mode of Adminastration | Adverse Effects(AEs) | Serious Adverse Effects (SAEs) | Outcome |
| Van de Donk et al., 2019 [17] | Fibromyalgia | Randomized placebo-controlled 4-way crossover trial 25 pts |
4 days | THC 22%/CBD < 1% T.D. 13.4 mg/1 mg, THC 6.3%/CBD 8% T.D. THC 13.4 mg/CBD 17.4 mg THC < 1%/CBD 9% T.D. 1 mg/18.4 mg Placebo |
Vp | Sore throat, bad taste, nausea (1/3 of pts). Cough (2/3 of pts). | No | Increase in pressure pain threshold. No analgesic effect. |
| Wilsey et al., 2016 [22] |
Spinal cord trauma or disease | Randomized, double-blind, placebo-controlled, crossover design study 42 pts |
3 days | THC 2.9%, THC 6.7%, placebo minimum dose: 400 mg of cannabis. |
Vp | H.D.: hungry ad memory disorders with more intensity than L.D. L.D.: high, stoned, sedated, changes in perceiving space, confused, minor attention. No withdrawal |
No | Reduction in pain intensity. No significant difference in pain relief between the higher and lower dose |
| Wallace et al., 2015 [20] |
Diabetic neuropathy | Randomized, double-blinded, placebo controlled crossover study 16 pts |
4 days | THC 1%, 4%, 7% or placebo Each dose: 400 mg of cannabis |
Vp | Euphoria with H.D. and M.D. Somnolence with the high dose group. No withdrawals |
No | Dose-dependent reduction in the intensity of spontaneous and evoked pain. |
| Eisenberg et al., 2014 [21] |
Complex Regional Pain Syndrome, radiculopathy, pelvic neuropathic pain, Spinal cord injury | Single-dose, open-label design 8 pts |
1 day | THC 19.9%/CBD 0.1% CBN 0.2%; single dose: 15.1 mg ± 0.1 mg of cannabis flos |
Vp | Lightheadedness No withdrawals |
No | Effective for heterogeneous collection of neuropathic pain conditions studied. |
| Wilsey et al., 2013 [25] |
P.N.P.: CRPS type I, diabetic neuropathy, idiopathic peripheral neuropathy, post-herpetic neuralgia, brachial plexopathy, radiculopathy. C.N.P.: spinal cord injury, Multiple Sclerosis, thalamic pain |
Double-blind, placebo-controlled, crossover study 39 pts |
3 days | L.D. THC (1.29%), M.D. THC (3.53%), or placebo Cannabis dose = 0.8 g of per administration. |
Vp | M.D. high, stoned, sedation. Reduction of learning and memory. Light reduction during testing of psychomotor skills with the dominant hand. No withdrawals |
No | Analgesic efficacy with L.D. and M.D. |
| Smoked Admistration | ||||||||
| Reference | Indication | Design of the Study and No. of pts. | Period of Treatment | Dose | Mode of Administration |
Adverse Effects
(AEs) |
Serious Adverse Effects (SAEs) | Outcome |
| Corey-Bloom et al., 2012 [24] |
Multiple Sclerosis | Randomized, double-blind, placebo controlled crossover design 37 pts |
2 days | THC 4% or placebo | S | High, dizziness and fatigue. 5 participants withdrew. |
No | Beneficial effects for spasticity and pain associated with multiple sclerosis. |
| Ware et al., 2010 [26] |
Post-traumatic or post-surgical neuropathic pain | Randomized, double-blind, placebo-controlled, four period crossover design 23 pts |
20 days | THC 2.5%, 6.0%, and 9.4% or placebo. Single 25-mg dose three times daily for the first five days in each cycle |
S | H.D.: headache, dry eyes, burning sensation, dizziness, numbness and cough. | No | Reduction of pain intensity. Improvement of sleep, anxiety and depression. |
| Ellis et al., 2009 [27] |
HIV-associated distal sensory predominant polyneuropathy (DSPN) | A phase II, single group, double-blind, placebo-controlled, crossover trial 34 pts |
10 days | THC 1–8% or placebo Three times daily |
S | Concentration difficulties, fatigue, sleepiness or sedation, increased duration of sleep, reduced salivation, thirst, increased heart rate | Induction of psychosis. Intractable cough. 2 participants were withdrawn for safety reasons. |
Reduction of neuropathic pain intensity in HIV-associated DSPN |
| Wilsey et al., 2008 [28] |
Complex regional pain syndrome type I, spinal cord injury, multiple sclerosis, peripheral neuropathy |
Randomized, double-blinded, placebo-controlled, crossover design 38 pts |
3 days | THC 7%, THC 3.5% or placebo | S | H.D.: impairment in attention, learning and memory, and psychomotor speed. L.D. 3.5%: decline in learning and memory. No withdrawals |
No | Reduction of pain intensity. No differences were observed with the two doses. |
| Abrams et al., 2007 [29] |
HIV-associated sensory neuropathy | Prospective randomized placebo-controlled trial 55 pts |
12 days | THC 3.56% or placebo three times daily. | S | Anxiety, sedation, disorientation, paranoia, confusion, dizziness, nausea. No withdrawals |
No | Relief of chronic neuropathic pain. |
| Oral Adminstration | ||||||||
| Reference | Indication | Design of the Study and No. of pts. | Period of Treatment | Dose | Mode of Administration |
Adverse Effects
(AEs) |
Serious Adverse Effects (SAEs) | Outcome |
| Poli et al., 2018 [18] |
FM, radiculopathy, headache, arthritis, various form of neuropathic pain and other chronic pain conditions | Prospective non-randomized single-arm clinical trial 338 pts |
12 months | THC 19%, CBD < 1%. Starting dose 5 mg/d of THC; at 6 months dose was 10 mg/d. | D | Sleepiness and mental confusion. | No | Reduced pain intensity. Reduction in anxiety and depression. |
| Zajicek et al., 2012 [23] |
Multiple Sclerosis (MUSEC trial) | Double blind, placebo controlled, phase III study 277 pts |
12 weeks | THC 5–25 mg or placebo daily | C | Dizziness, disturbance in attention, balance disorder, somnolence, dry mouth, nausea, diarrhea, fatigue, urinary infection, disorientation. Cannabis: thirty pts withdrew due to AEs. |
Urinary tract infections, head injury, and interstitial lung disease. | Reduction of muscle stiffness |
| Zajicek et al., 2003 [30] |
Multiple sclerosis (CAMS study) | Randomised, placebo-controlled trial 630 pts |
15 weeks | 2.5 mg synthetic THC, 2.5 mg THC + 1.25 mg CBD, placebo. Max 25 mg THC daily |
C | Dizziness, dry mouth, diarrhoea in active groups. Cannabis: constipation. |
One pt died from pneumonia after 13 weeks in the THC group. | Some improvement in mobility as assessed by patients indicates a subjective clinical effect. |
| Killestein et al., 2002 [31] |
Multiple Sclerosis | Randomized, double-blind, placebocontrolled, twofold crossover study 16 pts |
12 weeks | THC, THC + 20–30% CBD, placebo. THC 2.5 mg twice daily for first two weeks, then dose was increased to 5 mg twice daily. |
C | Dry mouth, headache, dizziness, increased, spasticity, somnolence, ataxia, dry mouth, emotional lability No withdrawals |
Acute psychosis episode in one pt. | Results do not suggest therapeutic benefit of either THC or plant-extract treatment. |
| Vaporized, Smoking, and Oral Administration | ||||||||
| Reference | Indication | Design of the Study and No. of pts. | Period of Treatment | Dose | Mode of Administration |
Adverse Effects
(AEs) |
Serious Adverse Effects (SAEs) | Outcome |
| Ware et al., 2015 [19] |
Chronic non-cancer pain | Randomized, double-blind, placebo-controlled, four period crossover design 431 pts |
12 months | THC 12.5 ± 1.5% or placebo. Median daily dose cannabis = 2.5 g/d. |
S, C, and Vp | THC: headache, dry eyes, burning sensation, dizziness, numbness, cough. Cannabis: 10 pts withdrew due to AEs and 5 due to AEs and lack of efficacy. |
Not statistically significant | Cannabis users: a mean 50 mL decrease in FEV1 and a mean 1% decrease in the FEV1/FVC ratio over 1 year. |
THC = Tetrahydrocannabinol; CBD = cannabidiol; CBN: Cannabinol; Vp = vaporization; S = smoke; D = decoction; C = capsules; T.D. = total dose; H.D. = high dose; M.D. = medium dose; L.D. = low dose.