Table 5 Pain

 Martin-Sanchez, 2009 [58]

To Feb 2008; 3

Government

18

Chronic pain

I: Plant-derived and synthetic cannabinoids

C: Placebo

• Pain

• Euphoria

• Dysphoria

• Events linked to alterations in perception

• Events affecting motor function

• Events that altered cognitive function

Favors intervention for pain, euphoria, events linked to alternations in perception, events affecting motor function, and events that altered cognitive function. No statistically significant difference between groups for dysphoria.

M

 Nielsen, 2017 [80]

No date limits; search run on Oct 29, 2015; 4

Government

9

Chronic pain

I: Plant-derived or synthetic cannabinoids alone or with opioids

C: Placebo + opioids

• Analgesia

• Pain intensity

• Experimental pain

• Opioid-sparing effect

• Sleep

• Energy

• Social functioning

Favors intervention for analgesia. Favors control for opioid-sparing effect, but analysis of high-quality studies for this outcome shows unclear efficacy. Only one study included for all other outcomes

M

 Nugent, 2017 [32]

Inception–Mar 2017; 5

Government

75

Chronic pain in various conditions

I: Plant-derived cannabinoids

C: Placebo or NR

• Central NP

• NP

• Cancer pain

• Risk of short-term non-serious AEs

• Lung function

• Pulmonary effects

• Cardiovascular events

No statistically significant difference for NP in MS or cancer pain; favors intervention for NP in other conditions; reported SBS for risk of short-term AEs, lung function, pulmonary effects, cardiovascular events

M

 Deshpande, 2015 [41]

Searched in April 2014; 3

NR

6

Chronic non-cancer pain

I: Plant-derived cannabinoids

C: placebo

• Pain relief

• Pain reduction

• Effect on dose of other analgesics

• QoL

Favors intervention for NP; only one study included on dose of other analgesics; no statistically significant difference between groups for QoL

L

 Lynch, 2015 [68]

2010–Oct 2014; 10

NR

11

Chronic non-cancer pain: FM, medication overuse, MS, OA, diabetic and chemotherapy-induced neuropathy

I: All types of cannabinoids

C: Unclear for one analysis (placebo, ibuprofen, o ramitriptyline); placebo; ibuprofen; amitriptyline

• Analgesia

• Pain intensity

• Pain

• Analgesic intake and dependence

• Sleep

• Anxiety

• Sleep quality

• VAS and patient global assessment of change

• NP

• Muscle stiffness pain

• Serious AEs

Favors intervention for analgesia (cannabinoids vs. placebo.) Reported SBS for serious AEs. Only one study included for all other outcomes

L

 Aviram, 2017 [26]

1975–Jul 2015; 2

No funding

43

Chronic or postoperative pain

I: Plant-derived and synthetic cannabinoids

C: placebo

• NP

• Peripheral NP

• Chronic pain

• Postoperative pain

• Acute postoperative pain

Favors intervention for all types of pain except acute postoperative pain (favors control)

M

 Meng, 2017 [31]

To Mar 11, 2016; 6

Non-profit

11

Chronic NP

I: Plant-derived and synthetic cannabinoids

C: Placebo; dihydrocodeine

• NP

• Central NP

• Peripheral NP

• QoL

• Anxiety

• Satisfaction of participants

• QST profile

• Withdrawal due to AEs

Favors intervention for NP, QoL, satisfaction, and QST profile; reported SBS for central NP and withdrawal due to AEs (vs. placebo); no statistically significant difference between groups for peripheral NP (vs. placebo.) Reported SBS for mixed central and peripheral NP (vs. dihydrocodeine)

M

 Andreae, 2015 [42]

Searched Apr 23, 2014;4

Mixed

5

Chronic NP

I: Plant-based cannabis

C: placebo

• Peripheral NP

• Withdrawal due to AEs

Favors intervention for peripheral NP. Reported SBS for withdrawal due to AEs.

M

 Campbell, 2001 [65]

MEDLINE 1966, EMBASE 1974, and Cochrane to Oct 1999; Oxford pain database: 1950–1994; 4

NR

9

Pain

I: All types of cannabinoids

C: Placebo; codeine

• Nociceptive pain

• Postoperative pain

• Cancer pain

• Abdominal pain

• NP

• Spasticity

• Subjective improvement of MS symptoms

• Balance

• Withdrawal due to AEs

Favors intervention for nociceptive pain and postoperative pain (cannabinoids vs. placebo). No statistically significant difference between groups for nociceptive pain, postoperative pain, and cancer pain (cannabinoids vs. codeine). Reported SBS for withdrawal due to AEs (compared with both placebo and codeine.) Only one study included for all other outcomes

M

 Finnerup, 2015 [69]

Jan 1966–to Jan 31 2014; 5

Non-profit

9

Pain in MS, diabetes, allodynia, SCI,

I: Plant-derived cannabinoids

C: placebo

• NP (NNT for 30–50% pain reduction)

No statistically significant difference between groups

M

 Iskedjian, 2007 [62]

Inception to end of June 2006; 4

Industry

7

NP

I: Plant-derived cannabinoids

C: Placebo

• Pain

• Withdrawals due to AEs

• Dizziness

• Somnolence

• Headache

• Nausea

• Diarrhea

• Fatigue

Favors intervention for pain; unclear/indeterminate for all adverse effects

CL

 NICE, 2013 [90]

Searches conducted between Jul 17 and 31st and Aug 23rd and 29th of August; 10

NR

4

NP

I: Plant-derived cannabinoids

C: Placebo; “other drugs”; amitriptyline; pregabalin

• Pain

• Continuous pain

• Burning pain

• Patient reported global improvement

• Sleep

• Withdrawal due to adverse effects

• Dizziness or vertigo

• Drowsiness

• Fatigue

• Nausea

• Vomiting

• Burning pain

• Cognitive impairment

• Mood disturbance

• Dry mouth

Favors intervention for pain, continuous pain, withdrawal due to adverse effects, sleep, dizziness, or vertigo (cannabinoids vs. placebo). Favors control for pain (cannabinoids vs. other drugs). No statistically significant difference between groups for withdrawal due to adverse effects and dizziness or vertigo (cannabinoids vs. amitriptyline), drowsiness, fatigue, nausea, vomiting, burning pain, cognitive impairment, mood disturbance, dry mouth, 30% pain relief, global improvement. Reported SBS for sleep (vs. placebo or pregabalin).

M

 Stevens, 2017 [38]

To Aug 20, 2016; 3

No funding

7

Acute pain

I: Cannabinoids (not specified)

C: Placebo

• Acute pain

• Total/average AEs

• Withdrawal due to AEs

No statistically significant difference between groups; AEs reported SBS

M