Table.

Analysis of nine randomised controlled trials of effectiveness of cannabinoids for three types of pain (cancer pain, chronic non-malignant pain, and postoperative pain)

Trial	Study chacterisitcs	Quality score (randomisation, blinding, withdrawals)	Intervention (oral unless indicated otherwise)		Efficacy data				Adverse drug reactions		Comments
					Pain relief (total pain relief or AUDC)	Pain intensity (SPID orVAS)	Other		Quantitatively	Qualitatively
Cancer pain
Jochimsen et al21	n=37 (35 analysed); crossover design; pain: cancer (moderate baseline pain); follow up 6 hours	1, 2, 0	BPP 2 mg x 1; BPP 4 mg x 1; codeine 60 mg x 1; codeine 120 mg x 1; placebo x 1		Complete: BPP 2 mg 2/35; BPP 4 mg 3/35; codeine 60 mg 9/35; codeine 120 mg 8/35; placebo 4/35	Reduced: BPP 2 mg 19/35; BPP 4 mg 20/35; codeine 60 mg 25/35; codeine 120 mg 31/35; placebo 25/35				11 item self assessment scale showed no difference in psychotomimetic effect. Sedation for both doses of BPP similar to both doses of codeine. No difference in blood pressure, heart rate, psychiatric interview	37 patients entered, 35 completed ( no reason given for 2 who did not complete); analgesic effect of codeine 120 mg better than placebo, BPP 4 mg worse than placebo; adverse effects not significantly different
Noyes et al22	n=10 (9 analysed); crossover design; pain: cancer (moderate baseline pain); follow up 6 hours	1, 2, 0	THC 5 mg x 1; THC 10 mg x 1; THC 15 mg x 1; THC 20 mg x 1; placebo x 1		Total (mean±SE): THC 5 mg 4.7±0.95; THC 10 mg 4.4±0.98; THC 15 mg 5.8±0.84; THC 20 mg 10.8±1.19; placebo 5.1±1.65;	SPID (mean±SE): THC 5 mg 2.6±0.53; THC 10 mg 1.4±0.42; THC 15 mg 3.6±0.65; THC 20 mg 4.6±0.66; placebo 0.9±0.3	Progressive pain relief with increasing doses of THC (P<0.001)		No of reactions per 10 patients: THC 5 mg 37; THC 10 mg 47; THC 15 mg 64; THC 20 mg 70; placebo 16	Progressive sedation and mental clouding (THC 20 mg caused heavy sedation in all patients); reduced blood pressure and heart rate; euphoria in 2 patients receiving THC 15 mg and 20 mg, 1 of whom was the only experienced marijuana user	Dose response for analgesia and adverse effects with THC
Noyes et al23	n=36 (34 analysed); crossover design; pain: cancer (moderate baseline pain); follow up 7 hours	1, 2, 0	THC 10 mg x 1; THC 20 mg x 1; codeine 60 mg x 1; codeine 120 mg x 1; placebo x 1		Total (mean±SE): THC 10 mg 9.8±1.40; THC 20 mg 12.9±1.46; codeine 60 mg 9.4±1.38; codeine 120 mg 12.2±1.57; placebo 6.8±0.95; P<0.05=THC 20 mg and codeine 120 mg v placebo	SPID (mean±SE): THC 10 mg 2.9±0.62; THC 20 mg 4.7±0.65; codeine 60 mg 3.6±0.75; codeine 120 mg 4.3±0.78; placebo 1.9±0.44; P<0.05 for THC 20 mg and codeine 120 mg v placebo	Analgesic effect of THC in 5 hours, codeine in 3 hours		No of reactions per 34 patients: THC 10 mg 186; THC 20 mg 259; codeine 60 mg 120; codeine 120 mg 13; placebo 92. Withdrawal owing to reactions: THC 2; codeine or placebo 0	Reduced blood pressure with THC	THC 20 mg highly sedating and produced mental effects prohibiting its use. THC 10 mg was well tolerated and somewhat sedating, but only equipotent to codeine 60 mg
Staquet et al (study 1)24	n=30 (26 analysed); crossover design; pain: cancer (moderate baseline pain); follow up 6 hours	1, 2, 1	NIB 4 mg x 1; codeine 50 mg x 1; placebo x 1		No data	SPID (mean±SE): NIB 4.72±3.33; codeine 4.79±3.19; placebo 2.15±2.56; P<0.05 for NIB and codeine v placebo			Drowsiness (% of patients): NIB 40%; codeine 44%; placebo 21%	4 withdrawals unrelated to study drug
Staquet et al (study 2)24	n=15 (15 analysed); crossover design; pain: cancer (moderate baseline pain); follow up 6 hours	1, 2, 1	NIB 4 mg x 1; secobarbital 50 mg x 1; placebo x 1		No data	SPID (mean±SE): NIB 4.40±2.06; secobarbital 2.13±1.77; placebo 1.87±1.30; P<0.05 for NIB v secobarbital and placebo			Drowsiness: (% of patients): NIB 40%; secobarbital 33%; placebo 21%		Secobarbital did not reduce pain intensity more than placebo, indicating that hypnotic properties do not imply pain relief
Chronic non-malignant pain
Holdcroft et al25	n=1; n of 1 crossover design; pain: abdominal (Mediterranean fever); follow up 6 weeks	1, 2, 0	THC 10 mg x 5 capsules/day; placebo x 5 capsules/day (each treatment 1 week)		No data	VAS (ranges): THC 4.8-6.2 mm; placebo 5.5-6.1 mm; NS	Daily morphine consumption less in THC group (P<0.001)			Nausea and vomiting throughout study;dysphoria and irritability associated with placebo weeks	Experienced cannabis user able to identify THC capsules for first 4 weeks of trial
Maurer et al26	n=1; n of 1 crossover design; pain: spinal cord pathology; follow up 5 months	1, 2, 0	THC 5 mg x 18; codeine 50 mg x 18; placebo x 18		No data	VAS (50 mm scale): THC 25.6 mm; codeine 19.7 mm; placebo 34.3 mm; P<0.05 for THC and codeine v placebo	THC had only antispasticity effect			THC and codeine better than placebo for mood, sleep, concentration, control of micturition, global effect; no altered state of consciousness
Postoperative pain
Jain et al (phase 1)27	n=36 (36 analysed); parallel group design; pain: postoperative or trauma (moderate to severe pain); follow up 6 hours	1, 1, 1	Intramuscular: levonantradol 1.5 mg x 1; levonantradol 2.0 mg x 1; placebo x 1		AUDC: P<0.05 for levonantradol v placebo at each dose	AUDC: P<0.05 for levonantradol v placebo at each dose			No of patients with reactions: levonantradol 23/40; placebo 2/16	Drowsiness common
										Dry mouth, dizziness, and dysphoria uncommon
										Levonantradol: increased heart rate and reduced blood pressure (no dose response)
Jain et al (phase 2)27	n=36 (36 analysed); parallel group design; pain: postoperative or trauma (moderate baseline pain); follow up 6 hours	1, 1, 1	Intramuscular: levonantradol 2.5 mg x 1; levonantradol 3.0 mg x 1; placebo x 1		AUDC: P<0.05 for levonantradol v placebo at each dose	AUDC: P<0.05 for levonantradol v placebo at each dose

BPP=benzopyranoperidine;THC=9-delta-tetrahydrocannabinol; NIB=nitrogen analogue THC. 

AUDC=areas under the difference curves (sum of change from baseline to six hours for pain intensity, pain relief, and pain analgesic scores). 

SPID=summed pain intensity difference. 

VAS=visual analogue scale.