Clinical trials with cannabinoid-related medications in human disease
| Disease/Condition | Sample Size, Design, Target Symptoms | Compound (Dose) | Parameters Studied | Results | Adverse Effects | Reference |
|---|---|---|---|---|---|---|
| MS and SCI | ||||||
| MS | Nine patients, DB, PL, spasticity | THC (5- and 10-mg single-dose p.o.) | EMG, clinical | Improved spasticity score (objective) | Minimal | Petro and Ellenberger (1981) |
| MS | Eight patients, SB, PL, tremor, ataxia | THC (5 mg/6 h max three doses p.o.) | Clinical | Improved coordination and sense of well being, decreased tremor (subjective) | Subjective “high” in all patients | Clifford (1983) |
| MS | 13 patients, DB, PL, C, spasticity | THC (2.5–15 mg daily for 5 days p.o.) | Clinical, questionnaire | Reduced spasticity (subjective); objective function tests not improved | Common | Ungerleider et al. (1987) |
| MS | One patient, OL, spastic tetraparesis | Cigarette smoke marijuana (one cigarette) | Clinical, tremor recording, EMG | Reduced ataxia and spasticity (objective) | None | Meinck et al. (1989) |
| MS | 10 patients, DB, C, spasticity | Cigarette smoke marijuana (one cigarette; 1.54% THC) | Dynamic posturography, objective balance | Impaired posture and balance | Subjective unpleasant “high” in all patients | Greenberg et al. (1994) |
| MS | One patient, DB, PL, C, spasticity | Nabilone (1 mg/2 days for 16 wk p.o.) | Visual analog scales | Improved painful muscle spasms, mood and well being (subjective); reduced frequency of nocturia | Mild sedation | Martyn et al. (1995) |
| MS and SCI | Two patients, OL, spasticity | THC (10 or 15 mg p.o. or rectal) | Clinical | Improved walking ability and passive mobility, reduced rigidity, slight pain relief | Temporal deterioration in ability to concentrate and in mood | Brenneisen et al. (1996) |
| MS | One patient, PL, nystagmus | Cigarette smoke marijuana (inhaled) | Eye movement recording | Reduced nystagmus amplitude and improved visual acuity | None | Schon et al. (1999) |
| MS | 16 patients, DB, PL, C, spasticity | Plant extract of THC (2.5–5 mg b.i.d. for 4 wk p.o.) | Clinical, questionnaires, Ashworth score | No improvement in Ashworth scale, worsening global impression | 41 adverse events in 16 patients during plant extract treatment | Killestein et al. (2002) |
| MS and SCI | 24 patients, DB, PL, C, heterogeneous | Plant extract of THC and CBD 1:1 (2.5–120 mg/day for 2 wk sublingual) | Clinical, questionnaires | Improvement of bladder control, muscle spasms, and spasticity and pain relief (subjective) but no in Ashworth scale | 4 dropouts due to adverse events | Wade et al. (2003) |
| MS | 630 patients, DB, R, PL, spasticity | Cannabis extract (Cannador: 2.5 mg Δ9-THC + 1.25 mg CBD/capsule; Marinol: THC max 25 mg/day for 15 wk p.o.) | Clinical, questionnaires Ashworth score, Rivermead Mobility Index | No change in the Ashworth score, but improvement in the patient-reported spasticity, pain, and sleep quality; unexpected reduction in hospital admission for relapse in the treatment groups; in 12-mo follow-up, THC improved muscle spasticity measured by the Ashworth scale and the Rivermead Mobility Index | Minimal, similar to placebo | Zajicek et al. (2003, 2004) |
| MS | 57 patients, DB, R, PL, C, spasticity, various | Cannabis-based capsules (2.5 mg THC and 0.9 mg CBD; max dose 30 mg/day THC p.o.) | Self-report of spasm frequency and symptoms, Ashworth Scale, Rivermead Mobility Index, 10-m timed walk | Improved spasm frequency and mobility in the 37 patients who received at least 90% of their prescribed dose | Minor adverse events were slightly more frequent in treated group | Vaney et al. (2004) |
| MS | 14 patients, DB, PL, tremor | Cannabis extract (Cannador: 2.5 mg Δ9-THC + 1.25 mg CBD/capsule p.o. for 2 wk) | Tremor index, measured using a validated tremor rating scale | No effects on tremor | Minimal | Fox et al. (2004) |
| MS | 57 patients, DB, R, PL, C, spasticity, various | Cannabis-based capsules (2.5 mg THC and 0.9 mg CBD; max dose 30 mg/day THC p.o.) | Self-report of spasm frequency and symptoms, Ashworth Scale, Rivermead Mobility Index, 10-m timed walk | Improved spasm frequency and mobility in the 37 patients who received at least 90% of their prescribed dose | Minor adverse events were slightly more frequent in treated group | Vaney et al. (2004) |
| MS | 14 patients, DB, PL, tremor | Cannabis extract (Cannador: 2.5 mg Δ9-THC + 1.25 mg CBD/capsule p.o. for 2 wk) | Tremor index, measured using a validated tremor rating scale | No effects on tremor | Minimal | Fox et al. (2004) |
| MS | 160 patients, DB, PL, R, M, VAS score for each patient's most troublesome symptom | GW-1000 (Sativex) delivered by oromucosal spray (2.7 mg Δ9-THC and 2.5 mg CBD at each actuation) | VAS score for each patient's most troublesome symptom, Ashworth Scale | No significant difference in the Ashworth scale, tremor, and pain at 6 wk between the Sativex and placebo groups; improved VAS scores for spasticity | Minimal | Wade et al. (2004) |
| Pain (see also MS above) | ||||||
| Cancer | 10 patients, P, non-R, non-DB, pain | THC (5, 10, 15, or 20 mg p.o.) | Cancer-associated pain | Superior to PL | Common at higher doses | Noyes et al. (1975a) |
| Cancer | 34 patients, P, non-R, C, pain | THC (20 mg, codeine 120 mg p.o.) | Cancer-associated pain | Both superior to PL | Common with THC | Noyes et al. (1975b) |
| Cancer | 45 patients, DB, C, P, pain | NIB (4 mg, codeine 50 mg, secobarbital 50 mg) | Cancer associated pain | NIB equal to codeine, superior to secobarbital and PL | Common | Staquet et al. (1978) |
| Dental extraction | 10 patients, DB, R, PL | THC (0.022, 0044 mg, diazepam 0.157 mg/kg i.v.) | Surgical pain | THC superior to PL, inferior to diazepam | Not discussed | Raft et al. (1977) |
| FMF | One patient, DB, R, C | THC (50 mg daily p.o.) | Gastrointestinal pain | Superior to PL | Not discussed | Holdcroft et al. (1997) |
| MS | One patient, OL, pain | Nabilone (1 mg b.i.d. p.o.) | Questionnaire, various | Complete pain relief | None | Hamann and di Vadi (1999) |
| MS | 66 patients, DB, R, PL, pain, sleep disturbances | Sativex delivered by oromucosal spray (2.7 mg Δ9-THC and 2.5 mg CBD at each actuation) | Pain, sleep disturbances, numerical rating scale | Improved central neuropathic pain and sleep disturbances | Minimal | Rog et al. (2005) |
| Neuropathy of varying etiologies | 21 patients, DB, R, C, PL, pain | Ajulemic acid (CT-3, IP-751: 4 or 10 mg p.o. two times daily) | Neuropathic pain, VAS | Significant reduction of chronic neuropathic pain | Minimal | Karst et al. (2003) |
| HIV | 523 patients, cross-sectional questionnaire study | Cannabis | Questionnaire, various | In most patients who used cannabis to treat symptoms (143/523); reduction in muscle and neuropathic pain | Not discussed | Woolridge et al. (2005) |
| Anorexia-cachexia in patients with cancer, HIV, or AIDS | ||||||
| Cancer | 54 patients, R, DB, weight | THC (three doses of 0.1 mg/kg/day p.o.) | Appetite, weight | Improved appetite and increased weight | Dizziness, sedation, confusion | Regelson et al. (1976) |
| Cancer | 19 patients, OL, non-R, weight | THC (three doses of 5 mg/day p.o.) | Appetite, weight | Improved appetite, trends for weight increase | Common, but well-tolerated | Nelson et al. (1994) |
| HIV/AIDS | 10 patients, non-R, weight | THC (three doses of 2.5 mg/day p.o.) | Weight | Increased/stabilized weight | Mild | Gorter et al. (1992) |
| AIDS | 139 patients, R, PL, weight | THC (two doses of 2.5 mg/day p.o.) | VAS for hunger, weight | Improved VAS for hunger but not weight | Mild | Beal et al. (1995) |
| AIDS | 94 patients, non-R, OL, weight | THC (two doses of 2.5 mg/day p.o.) | VAS for hunger, weight | Improved VAS for hunger and weight (only for 1 month) | Sedation, psychosis, dysphoria | Beal et al. (1997) |
| AIDS | 52 patients, weight | THC (two doses of 2.5 mg/day p.o. +/- Megace) | VAS for hunger, weight | Less effective than Megace | Anxiety, euphoria, psychosis, confusion | Timpone et al. (1997) |
| Chemotherapy-induced nausea and vomiting | ||||||
| Chemotherapy-induced nausea and vomiting | Review of 30 randomized trials involving 1366 patients, nausea, vomiting | THC | Nausea, vomiting | Across all trials, cannabinoids were more effective than placebo | Various | Tramèr et al. (2001) |
| Traumatic brain injury | ||||||
| Closed head injury | 67 patients, R, DB, PL, phase II, M, neurological outcome | HU-211 (dexanabinol: 48 or 150 mg i.v.) | Intracranial, cerebral perfusion and blood pressure, Glasgow scale | Better intracranial pressure/cerebral perfusion pressure control, trends towards better neurological outcome | Similar in all groups, related to severe head trauma | Knoller et al. (2002) |
| Traumatic brain injury | 861 patients, R, PL, phase III, M, neurological outcome | HU-211 (dexanabinol: 150 mg i.v.) | Extended Glasgow scale at 6 months | No improvement | Similar in all groups, related to severe head trauma | Maas et al. (2006) |
| Parkinson's disease, levodopa-induced dyskinesia | ||||||
| Parkinson's disease | 24 patients, R, DB, PL, motor disability | SR141716 (0.3 mg/kg p.o.); antagonists of NK3 R (SR142801) and neurotensin receptors (SR48692) | Motor symptoms and levodopa-induced dyskinesias after a single dose of levodopa | No improvement in parkinsonian motor disability with any of drugs tested | Minimal | Mesnage et al. (2004) |
| Parkinson's disease | Seven patients, R, DB, PL, C, motor disability | Nabilone | Motor symptoms | Reduces levodopa-induced dyskinesia in PD | Minimal | Sieradzan et al. (2001) |
| Alzheimer's disease, dementia | ||||||
| Alzheimer's disease, dementia | Six patients, OL, pilot, neuropsychiatric symptoms | Dronabinol (2.5 mg/day for 2 wk) | Neuropsychiatric Inventory score, subscores for agitation, aberrant motor, and nighttime behaviors | Significant improvement in Neuropsychiatric Inventory total score, subscores for agitation, aberrant motor, and nighttime behaviors | Minimal | Walther et al. (2006) |