The research studies in the table below were each evaluated using the GRADE scale (
Cochrane Methods Bias, n.d
; “Cochrane Methods Bias. (n.d.). Assessing risk of bias in included studies. Retrieved from http://methods.cochrane.org/bias/assessing-risk-bias-included-studies
What is GRADE?, 2012
), a tool for assessing the quality of evidence, elucidating high, moderate, low, and very low evidence quality. All randomized experimental studies are initially rated as high quality; and observational studies began at low-quality rating. In this assessment, a study loses quality if it has serious risk of bias (from improper blinding of subjects and assessors, nonrandom sorting, patient dropout), confounding factors, imprecision, or inconsistency. Studies gain quality if the data show a large effect or dosage effect, or the study adequately controlled confounding factors.The table below presents the moderate- to high-quality data asserting a positive effect of cannabis for qualifying conditions. The table preferentially displays therapeutic effects. Adverse effects and/or the absence of effect are not included in this table except for when they add perspective to currently debated therapeutic applications. For example,
Hallak et al., 2010
detected no effect of CBD on schizophrenia symptomology. This is worth noting because CBD is often described as an antipsychotic (Russo and Guy, 2006
), though the details and applicability of this effect continue to be researched.The table groups the studies according to conditions with significant evidence and are preferentially grouped by qualifying condition. The conditions are listed in bold and subcategories are listed in italics. For example,
Freeman et al., 2006
, has data for Incontinence as a symptom of Multiple Sclerosis.The studies are not generalizable. The conclusions of the studies can only be applied to the particular symptoms, conditions, and groups that were studied. The Results column notes the condition, symptoms, and sex of the subjects with statistically relevant results. Many of the studies can apply to more than one qualifying condition; when this occurs, those studies are grouped based on the primary qualifying condition of study (i.e., Cachexia instead of HIV).
Tabled
1
| Study | Drug (Dosage), Delivery | Grade | Results |
|---|---|---|---|
| Cachexia | |||
Abrams et al., 2003 | Cannabis (3.95% THC three doses daily), smoked and dronabinol (3.93% three doses daily), oromucosal | Moderate to low | Smoked and oral cannabinoids not unsafe for HIV patients in short term. Increased weight by fat (smoked, p = 0.021; dronabinol, p = 0.004). Results applicable to male patients. N = 62 |
Andries et al., 2014 | Dronabinol (2.5mg twice daily), orally | Moderate to high | Significant weight gain of 1.00kg during dronabinol vs 0.34kg during placebo (p = 0.03). Results applicable to anorexic female patients. N = 25 |
Haney et al., 2005 | Dronabinol (10mg, 20mg, and 30mg), orally and cannabis (1.8%, 2.8%, and 3.9% THC), smoked | Moderate to low | Cannabis and dronabinol significantly increased caloric intake in the low BIA group (10mg and 1.8% THC p < 0.005, 30mg and 3.9% p < 0.01) but not in the normal BIA group. Results applicable to male patients. N = 29 |
Haney et al., 2007 | Cannabis (2.0%, 3.9% THC four times daily), smoked and dronabinol (5mg, 10mg four times daily), orally | High to moderate | Cannabis (3.9% THC) improved ratings of sleep (p < 0.005) in HIV patients. Dronabinol (p = 0.008) and cannabis (p = 0.01) dose dependently increased caloric intake by increasing the number of eating occasions, resulting in improved weight via fat gain. Results applicable to male patients. N = 10 |
Timpone et al., 1997 | Dronabinol (2.5mg twice daily), orally | Moderate to low | Megestrol acetate showed greater weight gain than dronabinol (p = 0.0001) and combining the two did not lead to additive weight gain in patients with HIV. N = 39 |
| Cancer | |||
Johnson et al., 2010
Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC: CBD extract and THC extract in patients with intractable cancer-related pain. Journal of Pain and Symptom Management. 2010; 39: 167-179 | THC:CBD (22mg–32mg/day THC, 20mg–30mg/day CBD), oromucosal | Moderate to low | THC:CBD caused 30% reduction in pain from baseline in patients unresponsive to opioids. THC:CBD patients used a median oral morphine dose lower than other treatments. THC:CBD had a significantly improved constipation score. (OR THC:CBD = 2.81, p = 0.006) N = 177 |
| Chronic Pain | |||
Narang et al., 2008 | Dronabinol (10mg and 20mg THC), orally | Moderate | Total pain relief at 8 hours (TOTPAR) improved (20mg p = 0.01, 10mg p = 0.05). Evoked pain (ESPID) decreased (20mg, 10mg p < 0.05). Significant reduction of pain over time (baseline vs week 2, p = 0.01; week 1 vs week 3, p = 0.05; week 2 vs week 4, p = 0.05). N = 30 |
| Rheumatoid Arthritis | |||
Blake et al., 2006 | Sativex (max 6 doses daily), oromucosal | Moderate to low | Improvements in morning pain on movement (p = 0.044), morning pain at rest (p = 0.018), quality of sleep (p = 0.027), (DAS28 p = 0.002), and pain at present (p = 0.016). Results applicable to female patients. N = 31 |
| Epilepsy | |||
| Dravet syndrome | |||
Devinsky et al., 2017 | CBD (20mg/kg/day), oromucosal | High to moderate | CBD decreased the median frequency of convulsive seizures per month (compared to placebo, p = 0.01). The Caregiver Global Impression of Change scale showed improvement in 62% of the CBD group (from baseline, p = 0.02). The frequency of total seizures of all convulsive types was reduced (p = 0.03). N = 120 |
| Lennox-Gastaut syndrome | |||
Thiele et al., 2018 | CBD (20mg/kg/day), orally | High | CBD decreased the median percentage of monthly drop by 43.9% (estimated median difference between placebo p = 0·013). Monthly frequency of total seizures decreased by a median of 41·2% from baseline with CBD (difference from placebo p = 0·0005). N = 171 |
| Fibromyalgia | |||
| Sleep | |||
Ware et al., 2010 | Nabilone (0.5mg daily), orally | High | Improved sleep over amitriptyline 10mg (Insomnia Severity Index, adjusted difference = -3.25; CI, -5.26 to -1.24), marginally better on restfulness (difference = 0.48; CI, 0.01 to 0.95). Results applicable to female patients. N = 29 |
| Pain | |||
Skrabek et al., 2008 | Nabilone (2mg daily), orally | Moderate to high | Significant decreases in the VAS (p < 0.02), Fibromyalgia Impact Questionnaire (p < 0.02), and anxiety (p < 0.02) at 4 weeks. N = 40* |
| HIV/AIDS | |||
| Neuropathy | |||
Abrams et al., 2007 | Cannabis (3.5% THC), smoked | Moderate | >30% reduction in pain from baseline (p = 0.04). 34% median reduction in chronic neuropathic pain (VAS p = 0.03). >30% reduction in pain was reported by 52% in the cannabis group (comparable to oral drugs used for chronic neuropathic pain). Results applicable to male patients. N = 50 |
Ellis et al., 2009 | Cannabis (1%–8% THC), smoked | High | Decrease in pain intensity (Descriptor Differential Scale p = 0.02). 46% of cannabis patients achieved at least 30% pain relief. Results applicable to male patients. N = 27 |
| Multiple Sclerosis | |||
Aragona et al., 2009 | Sativex (average 15 doses daily), oromucosal | Moderate to low | Did not induce psychopathology and did not impair cognition. At dosages higher than those used, interpersonal sensitivity, aggressiveness, and paranoiac features might arise. N = 17 |
Collin et al., 2007 | Sativex (max 48 doses daily), oromucosal | Moderate | Spasticity improved (NRS p = 0.048) and 40% of patients achieved >30% benefit (p = 0.014). N = 184 |
Collin et al., 2010 | Sativex (max 24 doses daily), oromucosal | Moderate to low | In the per-protocol analysis, 36% achieved at least a 30% improvement in NRS spasticity scores (p = 0.04). N = 177 |
Corey-Bloom et al., 2012 | Cannabis (4% THC), smoked | High | Significant decrease in modified Ashworth (p = 0.001), subjective pain score (p = 0.008), and highness (p = 0.001). N = 30 |
Vaney et al., 2004
Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled, crossover study. Multiple Sclerosis. 2004; 10: 417-424 | Cannabis extract (2.5mg THC, 0.9mg CBD. Max 30mg THC daily), orally | Moderate | Lowered spasm frequency and improved mobility results not statistically significant. N = 57 |
Wade et al., 2004 | Sativex (2.5mg–120mg daily), oromucosal | Moderate to low | Spasticity reduced (VAS p = 0.001). Improvement in quality of sleep (p = 0.047), and Guy’s Neurological Disability scale scores (p = 0.048). N = 160 |
Wade et al., 2010 | Sativex (N/A), oromucosal | Moderate to low (pooled data) | ~1/3 of patients gain at least a 30% improvement from baseline. A greater proportion of treated patients responded to the treatment (OR = 1.62, p = 0.0073), treated patients reported greater improvement (OR = 1.67, p = 0.030). N = 666 |
Zajicek et al., 2003 | Cannabis extract (2mg–5mg THC, 1mg–25mg CBD per capsule), orally | High | Improvements in spasticity (Ashworth p = 0.01), pain (p = 0.002), sleep (p = 0.025), and spasms (p = 0.038). N = 657 |
Zajicek et al., 2012 | Cannabis extract (5mg–25mg THC daily), orally | High to moderate | Relief from stiffness after 12 weeks (OR 2.26, p = 0.004). Rating scales had significant difference in muscle stiffness, body pain, muscle spasms, sleep quality at week 4 and increasing significance on week 8 for stiffness and body pain, and an increase in significance for spasms in week 12, but a decrease in significance in sleep and body pain (became nonsignificant) in week 12 (all significance values at least p < 0.025). N = 277 |
| Multiple Sclerosis | |||
| Neuropathies | |||
Langford et al., 2013
A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. Journal of Neurology. 2013; 260: 984-997 | Sativex (max 12 doses daily), oromucosal | Moderate | At the end of the treatment, a significant difference in pain score (NRS p = 0.028) and sleep quality (NRS p = 0.015). N = 339 |
Turcotte et al., 2015 | Nabilone (1mg twice daily), orally | Moderate to low | Significant differences in pain intensity (VAS p = 0.01). Patient perceived benefit higher with nabilone and gabapentin (p < 0.05). Results applicable to female patients. N = 15 |
| Incontinence | |||
Freeman et al., 2006 | Cannabis extract (2.5mg THC with 1.25mg CBD or 2.5mg THC. Max 25mg daily), orally | High | Both treatments improved incontinence (cannabis extract, p = 0.005; THC, p = 0.039). Pad weight reduced in both treatments (p = 0.001). N = 630 |
Kavia et al., 2010 | Sativex (max 8 doses in 3 hr and 48 doses in 24 hr), oromucosal | Moderate to low | Patients failed to respond to anticholinergics before study. Significant differences in number of episodes of nocturia (p = 0.010), bladder capacity (Ordinary Bladder Capacity p = 0.001), number of voids/day (p = 0.001) total number of voids (p = 0.007), impression of change (Patient’s Global Impression of Change p = 0.005), number of daytime voids (p = 0.044). Size of effect was greater for more severely affected subjects. Results applicable to female patients. N = 135 |
| Chronic Pain | |||
Rog et al., 2005 | Cannabis extract (2.5mg THC with 2.5mg CBD. Max 48 doses daily), oromucosal | High to moderate | Improvements in pain (NRS-11, p = 0.005; Neuropathic Pain Scale, p = 0.044) and sleep disturbances (p = 0.003). Treatment effect comparable to tramadol and pregabalin in treatment of peripheral neuropathic pain. Results applicable to female patients. N = 66 |
Svendsen et al., 2004 | Dronabinol (max dose 10mg daily), orally | Moderate | Median spontaneous pain intensity lowered (p = 0.02) and pain relief score rose (p = 0.035). Number Needed to Treat = 3.5 (poor outcome) for 50% pain relief. N = 24 |
| Nausea/Vomiting | |||
Meiri et al., 2007 | Dronabinol (2.5mg–20mg daily), orally | Moderate to low | Nausea absence was significantly greater in active treatment groups (p < 0.05). Nausea intensity and vomiting/retching lowest with dronabinol. Dronabinol and ondansetron are similarly effective for chemotherapy-induced nausea and vomiting. Combination therapy with dronabinol and ondansetron was not more effective than either agent alone. N = 61 |
Söderpalm et al., 2001 | Cannabis (8.4mg and 16.9mg THC), smoked | High to moderate | Acute feelings of nausea were reduced (8.4mg p < 0.05, 16.9mg p < 0.01) and emesis was also decreased (p < 0.05). The higher dose of marijuana significantly reduced nausea at 20 min. However, its effects are very modest relative to ondansetron (p < 0.05). N = 13 |
| Neuropathies | |||
Frank et al., 2008 | Nabilone (max 2mg daily), orally | Moderate to low | Dihydrocodeine is a better analgesic than nabilone (VAS p = 0.01). A small number of patients responded well to nabilone. N = 96 (33 of the 96 dropped out) |
Karst et al., 2003 | CT3 (a potent analog of THC-11-oic acid) (max 40mg and 80mg daily), orally | Moderate | Reduced pain 3 hours after intake (VAS p = 0.02). N = 21 |
Nurmikko et al., 2007 | Sativex (max 48 doses daily), oromucosal | High to moderate | Significant decrease in pain (NRS p = 0.004). N = 125 |
Wallace et al., 2007 | Cannabis (4%, 8% THC), smoked | High | 4% THC produced delayed analgesia (Visual Analogue Scale of Pain Intensity p = 0.027), 8% THC cannabis produced an increase in pain (Visual Analogue Scale of Pain Intensity p = 0.009) after 45 minutes. N = 19 |
Ware et al., 2010 | Cannabis (2.5%, 6%, and 9.4% THC, three times daily), smoked | High | Participants receiving 9.4% reported a lower average daily pain intensity (NRS p = 0.023), improved ability to fall asleep (easier, p = 0.001; faster, p < 0.001; more drowsy, p = 0.003), and improved quality of sleep (less wakefulness, p = 0.01). Anxiety and depression were improved with 9.4% (EQ-5D questionnaire p < 0.05). N = 23 |
Wilsey et al., 2008 | Cannabis (7% THC or 3.5% THC), smoked | High | Decrease in pain (VAS p = 0.02). Equal anti-nociception at every time point with no difference between the doses over time (p = 0.95). Significant differences in measures of unpleasantness (p < 0.01) and global impression of change (p < 0.01). N = 38 |
Wilsey et al., 2013 | Cannabis (3.53% or 1.29% THC), vaporized | Moderate to high | 1.29% as effective as 3.53% THC in pain relief. Increasing cumulative analgesia over time (180 min p < 0.0001, 240 min p = 0.0004, 300 min p = 0.0018); analgesia remained stable afterward. Decreased levels of sharpness, burning, aching pain (both doses p < 0.001). 1.29% THC more effective for burning pain (p < 0.0001); significantly reduced aching more than the 3.53% THC and placebo (p < 0.0001). N = 39 |
| Diabetes | |||
Wallace et al., 2015 | Cannabis (1%, 4%, or 7% THC), vaporized | Moderate | There was a modest reduction in spontaneous pain (% reduction in pain: placebo, 61.2%; 1% THC, 66.7%; 4% THC, 70.3%; 7% THC, 65.5%, p < 0.001 for all). N = 16 |
| Posttraumatic Stress Disorder | |||
Jetly et al., 2015 | Nabilone (0.5mg–3mg at bedtime), orally | Moderate | Reduction in nightmares (CAPS Recurring and Distressing Dream scores p = 0.03), improved global impression of change (Clinical Global Impression of Change p = 0.05) and general well-being (General Well-Being Questionnaire p = 0.04). Results applicable to male patients. N = 10 |
| Schizophrenia | |||
Hallak et al., 2010 | CBD (300mg or 600mg), orally | Moderate | Single dose showed no effects on symptomology. N = 28 |
| Spinal Cord Injury | |||
Pooyania et al., 2010 | Nabilone (max 1mg daily), orally | Moderate to low | Decrease in the spasticity (Ashworth “most involved muscle group” p = 0.003) and total Ashworth (p = 0.001). N = 11 |
| Tourette Syndrome | |||
Müller-Vahl et al., 2002 | THC (5mg, 7.5mg, 10mg), orally | Moderate to low | Significant improvement of self-reported tics (Tourette’s Syndrome Symptom List p = 0.015) and obsessive compulsive behavior (p = 0.041). Objective scores showed improvement in simple motor tics (p = 0.026), complex motor tic (p = 0.015), all motor tics (simple and complex motor tics) (p = 0.026), and complex vocal tics (p = 0.041). Results applicable to male patients. N = 12 |
Notes
- 1.Brand-name and generic-name drug dosages:
- •Sativex (2.7mgTHC, 2.5mg CBD)
- •Dronabinol (2.5, 5, or 10mgTHC)
- •Nabilone (1mgTHC)
- •
- 2.If dosage schedule is not mentioned (i.e., daily, twice daily, at bedtime, max in 24 hr), then the study only assessed a single dose.
- 3.An effect is considered statistically significant if the p value is greater than or equal to 0.05. Other significant effects are noted by confidence intervals, effects, and ratios (Page, 2014).
- 4.If more than 75% of patients in a study are one sex, then results are applicable to that sex. An * denotes that sex proportion of patients is not given.
Abbreviations
BIA = bioelectrical impedance analysis; CBD = cannabinol; CI = Confidence Interval; DAS = Disease Activity Score; NRS = Numerical Rating Scale; OR = Odds Ratio; VAS = Visual Analogue Scale; THC = tetrahydrocannabinol
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