Table 1.
Clinical Research Studying the Effect of Cannabidiol on Opioid Withdrawal Related Symptomatology
| Study | Population | CBD products | Outcome measures | CBD effect |
|---|---|---|---|---|
| Anxiety, restlessness, and irritability | ||||
| Crippa et al. (2004)43 | 10 healthy volunteers | Single dose of 400 mg oral CBD 99.9% pure powder (THC-Pharm, Frankfurt, Germany) dissolved in corn oil or placebo |
VAMS Regional cerebral blood flow was measured with 99mTc-ECD SPECT |
Decrease in anxiety Increase in sedation |
| Fusar-Poli et al. (2009)48 | 15 healthy male volunteers | Single dose of either 10 mg THC capsule 99.6% pure, 600 mg CBD capsule 99.9% pure (THC-Pharm, Frankfurt, Germany) or placebo | Brain BOLD and skin conductance in response to fearful faces. VAMS | Decrease in anxiety |
| Bhattacharyya et al. (2010)41 | 15 healthy men | Single dose of either 10 mg THC capsule 99.6% pure, 600 mg CBD capsule 99.9% pure (THC-Pharm, Frankfurt, Germany and STI Pharmaceuticals Ltd) or placebo | Brain BOLD and skin conductance response while participants performed a verbal memory task, viewing fearful faces, a response inhibition task (Go No-Go) and a visual and auditory stimulation task. VAMS |
Decrease in anxiety |
| Martin-Santos et al. (2012)52 | 16 healthy men | Single dose of either 10 mg THC capsule 99.6% pure, 600 mg CBD capsule 99.9% pure (THC-Pharm, Frankfurt, Germany and STI Pharmaceuticals Ltd) or placebo | PANSS VAMS STAI-S |
CBD had no difference to placebo |
| Das et al. (2013)49 | 48 healthy volunteers | Single dose of 32 mg CBD (STI pharmaceuticals, United Kingdom) in 0.08 mg ethanol vehicle vaporized using a Volcano Medic vaporizer (Storz & Bickel, Tuttlingen, Germany) or placebo | Skin conductance and shock expectancy measures | CBD enhanced consolidation of extinction learning |
| Arndt and de Wit (2017)50 | 38 healthy volunteers | Single dose of 300, 600, and 900 mg oral solution (300 mg/mL solution; Insys Therapeutics) or placebo vehicle | Heart rate Blood pressure POMS VAS for Drug Effects Questionnaire Emotional Stroop Rating of positivity and negativity to affective pictures The DEIT ABT Measure of social acceptance and ostracism (Cyberball task) |
Minimal behavioral and subjective effects |
| Zuardi et al. (2017)46 | 60 healthy volunteers | Single dose of 100, 300, and 900 mg oral capsule (99.6% pure CBD powder dissolved in corn oil; BSPG-Pharm, United Kingdom), clonazepam, or placebo | VAMS | Decrease in anxiety with 300 mg dose, but not 100 or 900 mg. |
| Linares et al. (2019)44 | 57 healthy volunteers | Single dose 150, 300, and 600 mg oral capsules 99.9% pure CBD (STI-Pharm, United Kingdom) dissolved in corn oil or placebo | VAMS | 300 mg CBD decreased anxiety |
| Bergamaschi et al. (2011)40 | 24 patients with social anxiety disorder | Single dose of 600 mg oral capsule (∼99.9% pure CBD dissolved in corn oil supplied by STI-Pharm, United Kingdom and THC-Pharm, Germany), or placebo | VAMS SSPS-N |
Decrease in anxiety |
| Crippa et al. (2011)42 | 10 patients with social anxiety disorder | Single dose of 400 mg oral capsule (99.9% pure CBD from THC-Pharm, Germany dissolved in corn oil) or placebo | SPECT imaging VAMS |
Decrease in anxiety |
| Hundal et al. (2018)51 | 32 participants with high paranoid traits | Single-dose 600 mg oral capsules (Synthetic CBD capsules (100 mg) from GW Pharmaceuticals, United Kingdom) or placebo | The University of Wales Mood Adjective Checklist Beck's Anxiety Inventory | No evidence of any benefit of CBD in anxiety or persecutory ideation |
| Masataka (2019)45 | 37 teenagers with social anxiety disorder and avoidant personality disorder | 4 weeks of daily doses of 300 mg oral CBD (RSHO-X Hemp Oil that did not contain other cannabinoids or terpenes from HempMeds) or placebo | Fear of Negative Evaluation Questionnaire Liebowitz Social Anxiety Scale |
Decrease in anxiety |
| Appiah-Kusi et al. (2020)39 | 26 healthy controls and 32 clinically high risk for psychosis | Daily dose of 600 mg daily for 1 week (STI Pharmaceuticals, United Kingdom) or placebo | SSPS-N TSST Blood cortisol level |
CBD group had an intermediate response to anxiety, experience of public speaking stress and change in cortisol associated with experimental stress exposure |
| Pain, arthralgias, and myalgias | ||||
| Sexton et al. (2016)55 | 1429 medical cannabis users | Various cannabis products | Self-reports on Pain Anxiety Depression Headache/migraine Nausea Muscle spasticity |
Survey respondents reported an average of 86% reduction in symptoms as a result of cannabis use |
| Wade et al. (2003)56 | 24 patients with intractable neurogenic pain symptoms | Daily use of pump-action sublingual spray that delivered whole-plant extracts of 2.5 mg THC and/or CBD with each actuation (GW Pharmaceuticals, United Kingdom) or placebo for 2 weeks each | VAS for pain NRS for spasticity |
Decreased pain, decreased spasticity |
| Notcutt et al. (2004)65 | 34 chronic pain patients | 2.5 mg of THC, 2.5 mg CBD, 2.5 mg THC +2.5 mg CBD whole plant extracts (GW Pharmaceuticals, United Kingdom) or placebo in aerosol or pump action sprays | BDI General Health Questionnaire 28 VAS for pain Sleep duration (hours), and quality of sleep (good, fair, poor) |
CBD monoproducts had little benefit |
| Cuñetti et al. (2018)62 | 7 kidney transplant patients with chronic pain | Increasing twice a day dose of 50–150 mg/day whole plant extract CBD Charlotte's Web, in oral solution from Stanley Brothers Social Enterprises (Colorado Springs, CO) orally for 3 weeks | Self-report pain scores | Two patients had total pain improvement, four had partial improvement, and one had no change |
| van de Donk et al. (2019)66 | 20 chronic pain patients with fibromyalgia | Single vapor inhalations of four strains of cannabis -22.4-mg THC and <1-mg CBD -13.4-mg THC and 17.8-mg CBD -18.4-mg CBD and <1-mg THC -Placebo All products from Bedrocan International BV (Veendam, the Netherlands) |
VAS for pain | There was a small analgesic response after single inhalation of the 13.4-mg THC and 17.8-mg CBD cannabis strain |
| Gulbransen et al. (2020)63 | 400 patients with noncancer chronic pain | Self-titrated daily dose 100 mg CBD/mL oil in 25 mL bottles taken orally (Tilray CBD100, Tilray, Nanaimo, Canada) | EQ-5D-5L questionnaire EQ VAS |
Improvements in pain/discomfort and anxiety/depression |
| Xu et al. (2020)64 | 29 patients with peripheral neuropathy | Up to four times a day application of CBD topical cream containing 250 mg/3 fl. oz (Theramu Relieve CBD compound cream Bakersfield, CA) or placebo | Neuropathic Pain Scale | Decreased pain |
| Capano et al. (2020)61 | 131 chronic pain patients | Daily dose of two 15 mg, CBD-rich hemp-derived soft gels (contained 15.7 mg CBD, 0.5 mg THC, 0.3 mg CBDV, 0.9 mg CBDA, 0.8 mg CBC, and >1% botanical terpene blend from Ananda Professional) for 8 weeks | PDI-4 PEG Scale assessing Pain Intensity and Interference PSQI Prescribed opioid dose |
Decreased pain, improved sleep quality, 53% of patients decreased or eliminated their prescribed opioid use |
| Craving | ||||
| Hurd et al. (2019)31 | 42 drug-abstinent individuals with heroin use disorder | Daily dose of 400 or 800 mg (100 mg/mL; Epidiolex, GW Pharmaceuticals, United Kingdom), or placebo for 3 consecutive days | VAS for Craving and Anxiety | Decrease in cue-induced craving and anxiety |
| Abdominal cramps, nausea, vomiting and diarrhea | ||||
| Grimison et al. (2020)77 | 81 patients with chemotherapy-induced nausea and vomiting | 1–4 self-titrated capsules of oral THC 2.5 mg/CBD 2.5 mg cannabis extract (TN-TC11M Tilray, Canada) three times daily, from days −1 to 5, or placebo | Self-reported experience of nausea and vomiting, use of rescue medications, and dose of study medication. Functional Living Index-Emesis | THC:CBD improved nausea and vomiting |
| Insomnia | ||||
| Linares et al. (2018)73 | 27 healthy volunteers | 300 mg CBD capsule (99.9% purity without THC from STI-Pharm, Brentwood, United Kingdom) or placebo |
Polysomnography VAMS State-Trait Anxiety Inventory Epworth Sleepiness Scale PSQI Psychomotor Vigilance Test |
No interference with sleep cycle or no change in cognitive or subjective measures |
| Carlini and Cunha (1981)70 | 15 individuals with insomnia | Once a week dose of either CBD 40, 80, 160 mg (crystalline CBD supplied by the National Institutes of Health), placebo, and 5 mg nitrazepam | 10-point questionnaire on sleep, sleep quality, dream recall, and reawakening | 160 mg dose of CBD increased amount of sleep. All doses of CBD resulted in less dream recall. |
| Fleury-Teixeira et al. (2019)72 | 18 patients with autism spectrum disorder | CBD-enriched Cannabis extract with a CBD to THC ratio of 75:1 capsules containing 25 or 50 mg CBD and 0.34 or 0.68 mg THC (CBDRx) for 6–9 months | Symptoms of autism spectrum disorder reported by parents/caregivers | Improvement in sleep problems |
| Barchel et al. (2019)71 | 53 children with autism spectrum disorder | Daily dose of cannabinoid oil solution containing CBD 16 mg/kg with maximal daily dose 600 mg, and for THC 0.8 mg/kg with maximal daily dose of 40 mg (Tikun Olam, Inc., Israel) | Specialists assessed participants for four autism spectrum disorder comorbidities (hyperactivity symptoms, sleep problems, self-injury and, anxiety) at baseline. Then biweekly telephone interviews with parents |
For 21 children with difficulty sleeping, sleep problems improved in 71.4% and worsened in 4.7% |
| Shannon et al. (2019)47 | 72 adults total (n=42 with anxiety and n=25 with poor sleep) | Daily dose of 25,50, or 75 mg CBD oral capsule (CV Sciences, Inc.) | PSQI Hamilton Anxiety Rating Scale |
Improvements in anxiety and sleep quality |
| Tremors | ||||
| de Faria et al. (2020)89 | 24 patients with Parkinson's disease | Single dose crossover 300 mg 99.9% pure CBD powder (BSPG-Pharm, United Kingdom) dissolved in corn oil and packaged in gelatin capsules or placebo | VAMS Tremors measured by an accelerometer |
Decrease in tremor amplitude Decrease in anxiety |
| Muscle spasms | ||||
| Wade et al. (2004)86 | 160 patients with multiple sclerosis | THC:CBD 1:1 oromucosal spray (Sativex) or placebo for 6 weeks, then optional THC:CBD 1:1 oromucosal spray for 4 additional weeks (GW Pharma, United Kingdom) | VAS for spasticity | Improvement in spasticity |
| Wade et al. (2006)85 | 137 patients with multiple sclerosis | THC:CBD 1:1 oromucosal spray (Sativex) or placebo for 10 weeks (GW Pharma, United Kingdom) | VAS for spasticity, diary scores of main symptoms | Improvement in spasticity |
| Collin et al. (2007)80 | 189 patients with multiple sclerosis | THC:CBD 1:1 oromucosal spray (Sativex) or placebo for 6 weeks (GW Pharma, United Kingdom) | NRS for spasticity | Improvement in spasticity |
| Collin et al. (2010)81 | 337 patients with multiple sclerosis | THC:CBD 1:1 oromucosal spray (Sativex) or placebo for 15 weeks (GW Pharma, United Kingdom) | NRS for spasticity | Improvement in spasticity |
| Novotna et al. (2011)84 | 572 patients with multiple sclerosis | THC:CBD 1:1 oromucosal spray (Sativex) or placebo for 19 weeks (GW Pharma, United Kingdom) | NRS for spasticity | Improvement in spasticity |
| Notcutt et al. (2012)83 | 36 patients with multiple sclerosis | THC:CBD 1:1 oromucosal spray (Sativex) or placebo for 6 weeks (GW Pharma, United Kingdom) | Time to Treatment Failure, Carer Global Impression of Change, Subject Global Impression of Change | Improvement in spasticity |
| Tachycardia and hypertension | ||||
| Jadoon et al. (2017)88 | 9 healthy male volunteers | Single dose of 600 mg Epidiolex (GW Pharmaceuticals, United Kingdom) or placebo | Finometer and laser Doppler flowmetry for cardiovascular monitoring | Decreased blood pressure Increased heart rate |
| Sultan et al. (2020)87 | 26 healthy male volunteers | Daily dose of 600 mg CBD or placebo for 7 days Phivida Neutrafuels (Phivida Organics) | Finometer and brachial site pulse wave analysis for cardiovascular monitoring | Decrease in blood pressure |
| Depression | ||||
| Beale et al. (2018)94 | 20 cannabis users | 50 mg CBD oral capsules (99.5% pure crystalline herbal origin CBD in Miglyol 812 and Softisan 378 from Trigal Pharma Ltd. and BioSynthesis Pharma Group Ltd.) Twice daily dose of two capsules×10 weeks |
Structural MRI scan | CBD may be therapeutic for clinical disorders characterized by hippocampal pathology including depression |
| Solowij et al. (2018)95 | 20 cannabis users | 50 mg oral capsules (99.5% pure crystalline herbal origin CBD in Miglyol 812 and Softisan 378 from Trigal Pharma Ltd. and BioSynthesis Pharma Group Ltd.) Twice daily dose of two capsules×10 weeks |
BDI | Decreased depressive symptoms |
| Fatigue | ||||
| Rosenberg et al. (2017)97 | 48 childhood epilepsy patients | Caregiver titrated daily dose of 99% CBD extract 100 mg/mL in sesame seed oil solution taken orally (GW Pharmaceuticals, United Kingdom) | Caregiver reported Quality Of Life for Childhood Epilepsy | Improvement in energy/fatigue |
| Mathur et al. (2020)96 | 371 patients with autoimmune hepatitis (n=93 respondents reported current or past use of CBD) | Nonspecified CBD products | Self-report on CBD and autoimmune hepatitis-related questions | 38% of CBD users reported fatigue as their reason for CBD use and the majority of these users reported a significant improvement in fatigue |
ABT, Attentional Bias Task; BDI, Beck Depression Inventory; BOLD, blood oxygenation level dependent; CB1, cannabinoid; CBC, cannabichrome; CBD, cannabidiol; CBDA, cannabidiolic acid; CBDV, cannabidivarin; DEIT, Dynamic Emotion Identification Task; EQ VAS, EuroQol Visual Analogue Scales; MRI, magnetic resonance imaging; NRS, Numerical Rating Scale; PANSS, Positive and Negative Psychotic Syndrome Scale; PDI-4, Pain Disability Index; PEG, Pain, Enjoyment, General Activity; POMS, Profile of Mood States; PSQI, Pittsburgh Sleep Quality Index; SPECT, Single Photon Emission Computed Tomography; SSPS-N, Self-Statements during Public Speaking Scale; STAI-S, Spielberger State Anxiety Inventory; THC, Tetrahydrocannabinol; TSST, Trier Social Stress Test; VAMS, Visual Analogue Mood Scale; VAS, Visual Analogue Scale.