TABLE 1.

Characteristics of the selected clinical trials.

Clinical trials with a POSITIVE outcome
Country		Study TITLE	Study type	Administration	Product	Condition	Number of patients
1	AUSTRALIA	A pilot randomised placebo-controlled trial of cannabidiol to reduce severe behavioural problems in children and adolescents with intellectual disability Efron et al. (2021)	Double-blinded Placebo-controlled Randomized	Oral (solution)	CBD	Severe behavioural problems (in children and adolescents with intellectual disability)	8
2	AUSTRALIA	Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial Grimison et al. (2020)	Double-blinded Multicentre Placebo-controlled Randomized	Oral (capsules)	Herbal Cannabis: THC:CBD (1:1 ratio) Cannabis sativa L. extract	Refractory chemotherapy-induced nausea and vomiting	80 enrolled 72 completed the study
3	AUSTRALIA	Cannabis use in patients 3 months after ceasing nabiximols for the treatment of cannabis dependence: Results from a placebo-controlled randomised trial Lintzeris et al. (2020)	Double-blinded Multicentre Placebo-controlled Randomized	Oro-mucosal spray	Sativex® (obtained from Cannabis sativa L.)	Cannabis dependence	128
4	AUSTRALIA	A Phase 1, Randomised, Placebo-Controlled, Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of Cannabidiol in Fed Healthy Volunteers Perkins et al. (2020)	Double-blinded Placebo-controlled Randomized	Oral (solution)	CBD	Safety, tolerability and pharmacokinetics evaluations on healthy volunteers	24
5	ISRAEL	The pharmacokinetics, efficacy, and safety of a novel selective dose cannabis inhaler in patients with chronic pain: A randomized, double-blinded, placebo-controlled trial Almog et al. (2020)	Double-blinded Placebo-controlled Randomized	Inhalation	Herbal Cannabis: Bedrocan® (22% THC, <1% CBD)	Chronic pain	27 enrolled 25 completed the study
6	ISRAEL	Pharmacokinetic investigation of synthetic cannabidiol oral formulations in healthy volunteers Izgelov et al. (2020)	Blinded	Oral (powder, oil or self-nano-emulsifying drug delivery system)	CBD	Oral absorption processes of synthetic CBD when given in different oral formulations in healthy volunteers	12
7	ISRAEL	The safety, tolerability, and effectiveness of PTL-101, an oral cannabidiol formulation, in pediatric intractable epilepsy: A phase II, open-label, single-center study Mitelpunkt et al. (2019)	Open-label	Oral (capsules)	CBD	Treatment-resistant epilepsy (in paediatric patients)	16 enrolled 11 completed
8	ISRAEL	Effect of adding medical cannabis to analgesic treatment in patients with low back pain related to fibromyalgia: an observational cross-over single centre study Yassin et al. (2019)	Observational	Inhalation	THC:CBD (1:4 ratio) herbal Cannabis	Low back pain related to fibromyalgia	31
9	SWITZERLAND	Cannabidiol enhances verbal episodic memory in healthy young participants: A randomized clinical trial Hotz et al. (2021)	Double-blinded Placebo-controlled Randomized	Inhalation	CBD	Verbal episodic memory in healthy young subjects	39
10	UNITED KINGDOM	Cannabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial Freeman et al. (2020)	Double-blinded Placebo-controlled Randomized	Oral (capsules)	CBD	Desire to stop using Cannabis	82
11	UNITED KINGDOM	Normalization of mediotemporal and prefrontal activity, and mediotemporal-striatal connectivity, may underlie antipsychotic effects of cannabidiol in psychosis O'Neill et al. (2021)	Double-blinded Placebo-controlled Randomized	Oral (capsules)	CBD	Psychosis	34 enrolled 32 completed
12	UNITED KINGDOM	Effects of cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder Pretzsch et al. (2019a)	Double-blinded Placebo-controlled Randomized	Oral (solution)	CBD	Brain excitation and inhibition systems	34
13	UNITED KINGDOM	The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD) Pretzsch et al. (2019c)	Double-blinded Placebo-controlled Randomized	Oral (solution)	CBD	Low-frequency activity and functional connectivity in the brain	34
14	UNITED KINGDOM	Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity Wall et al. (2019)	Double-blinded Placebo-controlled Randomized	Inhalation	Herbal Cannabis: Cannabis containing both THC and CBD; Cannabis containing THC	Human brain’s resting-state networks	17
15	United States	Food effect on pharmacokinetics of cannabidiol oral capsules in adult patients with refractory epilepsy Birnbaum et al. (2019)	Open-label	Oral (capsules)	CBD	Refractory epilepsy	11 enrolled 8 completed the study
16	United States	Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial Hurd et al. (2019)	Double-blinded Placebo-controlled Randomized	Oral (solution)	CBD	Drug cue–induced craving and anxiety in drug-abstinent individuals with heroin use disorder	50 enrolled 42 completed
17	United States	The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower extremities Xu et al. (2020)	Double-blinded Placebo-controlled Randomized	Topical (cream)	CBD	Peripheral neuropathy	29
18	United States	A randomized trial of medical cannabis in patients with stage IV cancers to assess feasibility, dose requirements, impact on pain and opioid use, safety, and overall patient satisfaction Zylla et al. (2021)	Placebo-controlled Randomized	Inhalation, oral, topical	A variety of formulations (also based on herbal Cannabis) with differing ratios of THC/CBD were provided depending on individual patient symptoms	Pain, opioid use, safety, and satisfaction in cancer patient	30
Clinical Trials With A NEGATIVE Outcome
Country		Title	Study Type	Administration	Administerd Product	Condition	Number Of Patients
1	AUSTRALIA	The CANBACK trial: a randomised, controlled clinical trial of oral cannabidiol for people presenting to the emergency department with acute low back pain Bebee et al. (2021)	Double-blinded Placebo-controlled Randomized	Oral (solution)	CBD	Low back pain	100
2	BRAZIL	Cannabidiol for COVID-19 Patients with Mild to Moderate Symptoms (CANDIDATE Study): A Randomized, Double-Blind, Placebo-Controlled Clinical Trial Crippa et al. (2021)	Double-blinded Placebo-controlled Randomized	Oral (solution)	CBD	COVID-19	105
3	UNITED KINGDOM	The acute effects of cannabidiol on the neural correlates of reward anticipation and feedback in healthy volunteers Lawn et al. (2020)	Double-blinded Placebo-controlled Randomized	Oral (capsules)	CBD	Neural correlates of reward anticipation and feedback	28 enrolled 24 completed the study
4	UNITED STATES	The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial Bonn-Miller et al. (2021)	Double-blinded Placebo-controlled Randomized	Inhalation	Herbal Cannabis: Cannabis containing 12% THC and <0.05% CBD; Cannabis containing 11% CBD and 0.50% THC; Cannabis containing 7.9% THC and 8.1% CBD	Posttraumatic Stress Disorder	80 enroled 76 completed stage I 74 completed stage II
5	UNITED STATES	Acute effects of cannabinoids on symptoms of obsessive-compulsive disorder: A human laboratory study Kayser et al. (2020)	Double-blinded Placebo-controlled Randomized	Inhalation	Herbal Cannabis: Cannabis containing THC 7% and CBD 0.18%; Cannabis containing 0.4% THC and 10.4% CBD	Obsessive-compulsive disorder	14 enrolled 12 completed the study

Clinical Trials With an INCONCLUSIVE Outcome
Country		Title	Study Type	Administration	Administerd Product	Condition	Number of patients
1	AUSTRALIA	Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People Anderson et al. (2021)	Controlled Randomized	Oral (capsules)	CBD	Anxiety disorders	6
2	AUSTRALIA	Model-based analysis on systemic availability of co-administered cannabinoids after controlled vaporised administration Liu et al. (2020)	Double-blinded Placebo-controlled Randomized	Inhalation	THC; CBD; THC + low-dose CBD; THC + high-dose CBD	Evaluate the active dosage	36
3	AUSTRALIA	A randomised controlled trial of vaporised Δ9-tetrahydrocannabinol and cannabidiol alone and in combination in frequent and infrequent cannabis users: acute intoxication effects Solowij et al. (2019)	Double-blinded Placebo-controlled Randomized	Inhalation	THC; CBD; THC + low-dose CBD; THC + high-dose CBD	Evaluate the acute intoxication effects	36
4	ISRAEL	Oral CBD-rich Cannabis Induces Clinical but Not Endoscopic Response in Patients with Crohn’s Disease, a Randomised Controlled Trial Naftali et al. (2021a)	Double-blinded Placebo-controlled Randomized	Oral (solution)	THC:CBD (1:4 ratio) herbal Cannabis	Crohn’s Disease	56
5	ISRAEL	Cannabis is associated with clinical but not endoscopic remission in ulcerative colitis: A randomized controlled trial Naftali et al. (2021b)	Double-blinded Placebo-controlled Randomized	Inhalation	Herbal Cannabis: Cannabis containing 16% THC and 0.1% CBD	Ulcerative colitis	32
6	ISRAEL	Cannabinoid treatment for autism: a proof-of-concept randomized trial Aran et al. (2021)	Double-blinded Placebo-controlled Randomized	Oral (solution)	THC:CBD (1:20 ratio) herbal Cannabis; purified CBD: THC (1:20 ratio)	Autism spectrum disorder in children and adolescents	150
7	NETHERLANDS	An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia Van de Donk et al. (2019)	Double-blinded Placebo-controlled Randomized	Inhalation	Herbal Cannabis: Bedrocan® (22% THC, < 1% CBD); Bediol® (6.3% THC, 8% CBD); Bedrolite® (9% CBD, <1% THC)	Pain in patients with fibromyalgia	20
8	UNITED KINGDOM	Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without Autism Spectrum Disorder (ASD): a single dose trial during magnetic resonance spectroscopy Pretzsch et al. (2019b)	Double-blinded Placebo-controlled Randomized	Oral (solution)	Cannabidivarin	Autism Spectrum Disorder	34
9	UNITED STATES	Effect of Inhaled Cannabis for Pain in Adults With Sickle Cell Disease. A Randomized Clinical Trial Abrams et al. (2020)	Double-blinded Placebo-controlled Randomized	Inhalation	Herbal Cannabis: Cannabis containing 4.4% THC and 4.9% CBD	Pain in patients with sickle cell disease	23
10	UNITED STATES	Effects of oral, smoked, and vaporized cannabis on endocrine pathways related to appetite and metabolism: a randomized, double-blind, placebo-controlled, human laboratory study Farokhnia et al. (2020)	Double-blinded Placebo-controlled Randomized	Inhalation and oral (food)	THC	Appetite and metabolism in healthy valuntaires	20
11	UNITED STATES	Effects of Hemp Extract on Markers of Wellness, Stress Resilience, Recovery and Clinical Biomarkers of Safety in Overweight, But Otherwise Healthy Subjects Lopez et al. (2020)	Double-blinded Placebo-controlled Randomized	Oral (solution)	CBD (from Herbal Cannabis oil extract)	Markers of wellness, stress resilience, recovery and clinical biomarkers of safety in overweight, but otherwise healthy subjects	65
12	UNITED STATES	Cognitive function and adaptive skills after a 1-year trial of cannabidiol (CBD) in a pediatric sample with treatment-resistant epilepsy Thompson et al. (2020)	Open-label	Oral (solution)	CBD	Cognitive function and adaptive skills in a paediatric patients with treatment-resistant epilepsy	38