. 2022 Oct 19;16(1):10–30. doi: 10.1111/cts.13425

TABLE 1.

Interventional studies investigating the efficacy (and safety) of low‐dose CBD

Citation	Study design	Participant population	CBD dose (mg)	Primary outcome(s)	Effect	Side effects (n incidence)
Studies involving doses of ≤60 mg CBD
Naftali et al. ³⁰	DB (PC); BSD	20 (12 M); 18–50 years Crohn's disease	10 mg/day; 8 weeks	Crohn's disease symptoms	No effect	Did not differ from placebo
Notcutt et al. ³¹	“N‐of‐1” DB (PC); WSD	34 (11 M); 47 ± 10 years chronic non‐cancer pain	≤15 mg/day; 2 × 1‐week periods	Pain	No effect	NS
Lopez et al. ³²	DB (PC); BSD	65 (33 M); 18–55 years overweight healthy volunteers	15 mg/day; 6‐weeks	Multiple metabolic, QOL, and sleep‐related outcomes	Increased HDL	Did not differ from placebo
Vela et al. ³³	DB (PC); BSD	136 (48 M); ~62 years hand osteoarthritis or psoriatic arthritis	20–30 mg/day; 12‐weeks	Pain	No effect	CBD group: ductal carcinoma (1) and lipotymia (1). Placebo group: Shoulder fracture (1) and malignant hypertension (1)
Hobbs et al. ³⁴	Open label (without controls)	5 (2 M); 34 ± 13 years Healthy volunteers	30 mg; SD (water soluble)	LPS‐induced inflammation in PBMCs	Positive	None reported. No effect of either CBD formulation on blood pressure.
Hobbs et al. ³⁴	Open label (without controls)	5 (2 M); 27 ± 5 years Healthy volunteers	30 mg; SD (lipid soluble)	LPS‐induced inflammation in PBMCs	Positive
Carlini and Cunha ²⁹ (experiment 6)	DB (PC); WSD	15 (NS) poor sleepers	40 mg; SD	Sleep quality (subjective)	No effect	NS
Isenmann et al. ³⁵	DB (PC); WSD	16 (NS); 24 ± 3 years Healthy volunteers	60 mg; SD	Exercise‐induced muscle damage	Positive	NS
Studies involving doses of >60–100 mg CBD
Chagas et al. ³⁶	DB (PC); BSD	21 (15 M); 64 ± 10 years Parkinson's disease	75 mg/day; 6‐weeks	Parkinson's disease symptoms	No effect	None reported
Carlini and Cunha ²⁹ (experiment 6)	DB (PC); WSD	15 (NS) Poor sleepers	80 mg; SD	Sleep quality (subjective)	No effect	NS
Zuardi et al. ³⁷	DB (PC); BSD	35 (17 M); ~22 years Healthy volunteers	100 mg; SD	Anxiety	No effect	NS
Studies involving doses of >100–200 mg CBD
Linares et al. ³⁸	DB (PC); BSD	45 M; ~24 years Healthy volunteers	150 mg; SD	Anxiety	No effect	NS
Crippa et al. ³⁹	DB (PC); BSD	45 M; 18–35 years Healthy volunteers	150 mg; SD (powder)	Anxiety and facial emotion recognition	No effect	NS
Crippa et al. ³⁹	DB (PC); BSD	45 M; 18–35 years Healthy volunteers	150 mg; SD (corn oil)	Anxiety and facial emotion recognition	No effect	NS
Cochrane‐Snyman et al. ⁴⁰	DB (PC); WSD	13 M; 22 ± 3 years Healthy volunteers	150 mg/day; 3‐days	Exercise‐induced muscle damage	No effect	NS
Carlini and Cunha ²⁹ (experiment 6)	DB (PC); WSD	15 (NS) Poor sleepers	160 mg; SD	Sleep quality (subjective)	Positive	NS
Arout et al. ⁴¹	DB (PC); WSD	17 (8 M); 32 ± 8 years Healthy volunteers	200 mg; SD	Experimentally induced pain	Positive	Did not differ from placebo
Freeman et al. ⁴²	DB (PC); BSD	59 (43 M); ~26 years Cannabis use disorder	200 mg/day; 4‐weeks	Cannabis abstinence	No effect	Did not differ from placebo
Solowij et al. ⁴³	Open label (without controls)	20 (16 M); ~25 years Regular cannabis users	200 mg/day; 10‐weeks	Psychological symptoms	Positive	None reported
Jadoon et al. ⁴⁴	DB (PC); BSD	13 (10 M); 57 ± 10 years Type 2 diabetes	200 mg/day; 13‐weeks	Serum HDL and cholesterol	No effect	No SAEs
Studies involving doses of >200–300 mg CBD
de Faria et al. ⁴⁵	DB (PC); WSD	24 (22 M); 64 ± 10 years Parkinson's disease	300 mg; SD	Anxiety and tremors	Positive	None reported
Linares et al. ³⁸	DB (PC); BSD	45 M; ~24 years Healthy volunteers	300 mg; SD	Anxiety	Positive	NS
Zuardi et al. ³⁷	DB (PC); BSD	35 (17 M); ~22 years Healthy volunteers	300 mg; SD	Anxiety	Positive	NS
Zuardi et al. ⁴⁶	DB (PC); BSD	20 (NS) Healthy volunteers	300 mg; SD	Anxiety	Positive	NS
Sahinovic et al. ⁴⁷	DB (PC); WSD	9 M; ~33 years Healthy volunteers	300 mg; SD	Exercise physiology and enjoyment	Positive ^a	None reported
Bolsoni et al. ⁴⁸	DB (PC); BSD	33 (8 M); ~33 years PTSD	300 mg; SD	PTSD symptoms	No effect	NS
Bolsoni et al. ⁴⁹	DB (PC); BSD	33 (8 M); ~33 years PTSD	300 mg; SD	PTSD symptoms	Positive	NS
Hallak et al. ⁵⁰	DB (PC); BSD	28 (18 M); NS Schizophrenia	300 mg; SD	Selective attention	No effect	NS
Linares et al. ⁵¹	DB (PC); WSD	26 (12 M); 29 ± 9 years Healthy volunteers	300 mg; SD	Sleep quality (objective)	No effect	NS
Arndt and de Wit ⁵²	DB (PC); WSD	38 (19 M); 24 ± 4 years Healthy volunteers	300 mg; SD	Response to negative emotional stimuli	No effect	None reported
de Alencar et al. ⁵³	DB (PC); WSD	19 (10 M); ~63 years Essential tremor	300 mg; SD	Upper limb tremors and motor function	No effect	None reported
Masataka ⁵⁴	DB (PC); BSD	37 (26 M); 18–19 years Social anxiety disorder	300 mg/day; 4‐weeks	Anxiety	Positive	NS
Crippa et al. ⁵⁵	Open label (with controls)	118 (39 M); ~33 years Healthcare workers during COVID pandemic	300 mg/day; 4‐weeks	Emotional exhaustion and burnout	Positive	Increased appetite on CBD (n = 5) vs. control (n = 14)
Yeshurun et al. ⁵⁶	Open label (historical controls)	48 (31 M); ~56 years Patients receiving alloHCT	300 mg/day; 37‐days	Incidence of GVHD	Positive	“CBD was well tolerated, and no SAEs were attributed to its consumption.”
Chagas et al. ³⁶	DB (PC); BSD	21 (15 M); 64 ± 10 years Parkinson's disease	300 mg/day; 6‐weeks	Parkinson's disease symptoms	Positive	None reported
de Meneses‐Gaya et al. ⁵⁷	DB (PC); BSD	31 M; ~33 years Crack‐cocaine dependence	300 mg/day; 10‐days	Crack‐cocaine withdrawal symptoms	No effect	Did not differ from placebo
Studies involving oral of >300 to 400 mg CBD
Pacheco, Souza et al. ⁵⁸	Open label (without controls)	13 (6 M); 33 ± 7 years Healthcare workers during COVID pandemic	330 mg/day; 4‐weeks	‘Burnout’, depression, anxiety and insomnia	Positive	Nausea (1) and gastric discomfort (1)
Zuardi et al. ⁵⁹	Open label (without controls)	6 (4 M); 59 ± 15 years Parkinson's disease and psychosis	150–400 mg/day; 4‐weeks	Psychotic symptoms	Positive	None reported
Crippa et al. ⁶⁰	DB (PC); WSD	10 M; 24 ± 4 years Social anxiety disorder	400 mg; SD	Anxiety	Positive	NS
Crippa et al. ⁶¹	DB (PC); BSD	10 M; 30 ± 5 years Healthy volunteers	400 mg; SD	Anxiety	Positive	NS
Bebee et al. ⁶²	DB (PC); BSD	100 (56 M); ~47 years Lower back pain	400 mg; SD	Pain	No effect	No differences in AEs: CBD (n = 35) vs. placebo (n = 42)
Arout et al. ⁴¹	DB (PC); WSD	17 (8 M); 32 ± 8 years Healthy volunteers	400 mg; SD	Experimentally induced pain	No effect	Stomach upset on CBD (n = 4) vs. placebo (n = 1)
Hurd et al. ⁶³	DB (PC); WSD	14 (12 M); 52 ± 8 Heroin use disorder	400 mg/day; 3‐days	Opioid craving and anxiety	Positive	CBD group: Chest pain (1), headache (1), eye irritation (1), and mild diarrhea (2). No SAEs reported
Freeman et al. ⁴²	DB (PC); BSD	59 (43 M); ~26 years Cannabis use disorder	400 mg/day; 4‐weeks	Cannabis abstinence	Positive	Mild AEs: CBD (n = 96) vs. placebo (n = 65). Moderate AEs: CBD (n = 8) vs. placebo (n = 9). No SAEs reported

Note: Those that were administered CBD only (i.e., no placebo) were considered “open label” regardless of the design used, as participants were aware that they would be receiving CBD. In the side‐effect column “None reported” refers to studies in which potential adverse events were addressed in the study but there were no adverse effects of CBD found. “Not specified” or NS, refers to studies in which potential adverse effects were not addressed by the study.

Abbreviations: AE, adverse event; alloHCT, allogeneic hematopoietic cell transplantation; BSD, between‐subjects design; CBD, cannabidiol; COVID, coronavirus disease; DB, double‐blind; GVHD, graft versus host disease; HDL, high density lipoproteins; LPS, bacterial lipopolysaccharide; M, male; NS, not specified; PBMC, peripheral blood mononuclear cells; PC, placebo‐controlled; PTSD, post‐traumatic stress disorder; QOL, quality of life; SAEs, serious adverse events; SD, single dose; WSD, within subjects design; y, years.

^{^a}

Statistical analyses were not performed; however, the study found sufficient evidence to suggest the effects of CBD on exercise enjoyment were worthy of further investigation.