. 2020 Feb 27;5(1):12–31. doi: 10.1089/can.2018.0073

Table 4.

Cannabidiol-Induced Immune Suppression in Animals In Vivo

Model	Disease model	Route, dose range, and duration/frequency^a	Major effects	Reference
Male CD-1 mice	sRBC	i.p.	Modest ↓antibody production	¹⁵⁵
		25 mg/kg
		4 days
Male DBA/2 mice	Collagen-induced arthritis	i.p. or oral	↓disease, ↓TNF-α and IFN-γ	^139b
		2.5–20 mg/kg for i.p.
		5–50 mg/kg for oral
		10 days
Male ICR mice	Carrageenan-induced inflammation	ethosome (CBD in ethosomal gel)	↓inflammation	¹⁹⁸
Male ICR mice	Carrageenan-induced inflammation	100 mg of ethosomal CBD (3%)	↓inflammation	¹⁹⁸
Male Wistar rats	Carrageenan-induced inflammation	Oral	↓disease, ↓prostaglandin (PGE₂)	¹⁹⁹
		5–40 mg/kg
		3 days
Female NOD mice	Diabetes	i.p.	↓disease incidence, ↓IL-12, TNF-α and IFN-γ, ↑IL-4	¹²³
		5 mg/kg/day
		10–20 injections
Female C57BL/6 mice	EL-4 leukemia growth	i.p.	↑apoptosis of tumor cells	^80b
Female C57BL/6 mice	EL-4 leukemia growth	12.5 or 25 mg/kg once	↑apoptosis of tumor cells	^80b
Male Wistar rats	Sciatic nerve pain or CFA-induced inflammation	Oral	↓pain, ↓TNF-α, ↓prostaglandin (PGE₂)	⁸⁸
		2.5–20 mg/kg
		7 days
Male Sprague-Dawley rats	Ischemia-reperfusion injury (myocardial)	i.p.	Modest ↓infarct size, ↓TNF-α	²⁰⁰
		5 mg/kg
		twice
C57BL/6J mice^c	Aβ inflammation	i.p.	↓IL-1β, ↓iNOS	¹¹⁷
		2.5 or 10 mg/kg
		7 days
Male BALB/c mice	Ovalbumin (asthma)	i.p.	↓serum antibodies, ↓IL-2, IL-4, and IFN-γ	^140b
		5–20 mg/kg
		once
Male ddY mice	Focal cerebral ischemia	i.p.	↓infarct size, ↓neutrophil MPO activity	^129b
		3 mg/kg
		various times surrounding occlusion
Female NOD mice	Diabetes	i.p.	↓disease incidence, ↓IL-6 and IL-12, ↑IL-4 and IL-10	^124b
		5 mg/kg/day
		5 injections per week for 4 weeks
Female B6C3F1 mice	sRBC	Oral	Modest ↓antibody production	^55b
		25–100 mg/kg/day
		5 days
Male ICR mice	DNBS colitis	i.p.	↓inflammation, ↓colon weight:length ratio, ↓iNOS, IL-1β, ↑IL-10	^95b
		1–10 mg/kg
		6 days
Male Wistar rats	None	i.p.	↓blood leukocytes and lymphocytes, ↓B, T and CTL cells, ↑NK and NKT cells	²⁰¹
		2.5 or 5 mg/kg
		14 days

Male CD-1 mice	Diabetes	i.p. or i.n.	↓diabetic pain, ↓density of microglial cells	^81b
		0.1–2 mg/kg i.n.
		1–20 mg/kg i.p.
		3 months
Male C57BL/6 mice	Streptozotocin-induced diabetes	i.p.	↓disease, ↓TNF-α, NF-κB activity, ICAM-1, VCAM-1, iNOS, p-p38, p-JNK, ↑p-AKT	^120b
		1–20 mg/kg
		11 weeks
Male Wistar rats	TNBS colitis	i.p.	Modest ↓disease, ↓colonic contractions, ↓neutrophil MPO activity	¹³⁰
		5–20 mg/kg
		once
Male Wistar rats	Cecal ligation and puncture	i.p.	↑disease survival	¹⁸⁴
		2.5–10 mg/kg
		once or up to 9 days
Female Sabra mice	Hepatic encephalopathy (bile duct ligation)	i.p.	Improved disease-associated cognitive impairments, ↓TNF-α	²⁰²
		5 mg/kg
		4 weeks
Male BALB/c mice	Ovalbumin (footpad)	i.p.	↓footpad swelling, ↓TNF-α and IFN-γ, ↑IL-10	¹⁸⁸
		1–10 mg/kg
		5 days
Male Swiss OFI mice	LPS i.p.	i.p.	↓mast cell infiltration, macrophage activation marker, ↓TNF-α	⁹⁶
		10 mg/kg
		twice
Female C57BL/6 mice	Experimental autoimmune hepatitis	i.p.	↓hepatic inflammation, ↓IL-2, TNF-α, IFN-γ, IL-6, IL-17A, IL-12, MCP-1 (CCL-2), and eotaxin, ↑MDSCs	^86b
		10–50 mg/kg
		once
Male C57BL/6 mice	Ischemia reperfusion injury (liver)	i.p.	↓hepatic inflammation, ↓MIP-1α, ICAM, MIP-2, TNF-α, NF-κB activity, ICAM-1, iNOS, p-p38, p-JNK	¹¹⁸
		3 or 10 mg/kg
		once
C57BL/6 mice^c	LPS i.v.	i.v.	↓vasodilation, leukocyte margination, and extravasation, ↓COX-2, TNF-α, and iNOS	¹²¹
		1 or 3 mg/kg
		once
Male C57BL/6 mice	LPS-induced pulmonary inflammation	i.p.	↓BALF lymphocytes, macrophages, and neutrophils, ↓TNF-α, IL-6, MCP-1 (CCL-2), and MIP-2	^125b
		0.3–80 mg/kg
		once
Male Wistar rats	Meningitis (Streptococcus pneumoniae)	i.p.	Improved disease-associated cognitive impairments, ↓TNF-α	²⁰³
		2.5–10 mg/kg
		once or up to 9 days
C57BL/6 mice^c	Cerulein (pancreatitis)	i.p.	↓disease, ↓TNF-α and IL-6, ↓neutrophil MPO	^128b
		0.5 mg/kg
		twice
Newborn pigs^c	Hypoxia-ischemic brain injury	i.v.	neuroprotection, ↓IL-1	^59b
		1 mg/kg
		once
Male Wistar rats	Ovalbumin (asthma)	i.p.	↓TNF-α, IL-6, IL-4, IL-5, and IL-13	^127b
		5 mg/kg
		twice
Male C57BL/6 mice	LPS-induced pulmonary inflammation	i.p.	↓inflammation, ↓BALF lymphocytes, macrophages, and neutrophils, ↓TNF-α, IL-6, MCP-1 (CCL-2), and MIP-2	¹³²
		20–80 mg/kg
		once
Female C57BL/6 mice	None	i.p.	↑MDSCs	^136b
		20 mg/kg
		once
Female C57BL/6 mice	Malaria (Plasmodium berghei)	i.p.	↓IL-6 and TNF-α	²⁰⁴
		30 mg/kg
		3–5 days
Male Sprague Dawley rats	Freund's Adjuvant (osteoarthritis)	Transdermal	↓inflammation, ↓TNF-α	²⁰⁵
		0.6–63.2 mg/day
		4 days
Male ICR mice	DNBS Colitis	i.p. or oral^d	↓colon weight:length ratio, ↓neutrophil MPO	¹³¹
		5–30 mg/kg for i.p. 10–60 mg/kg oral
		3 days
Female NOD mice	Type 1 diabetes	i.p.	↓disease	²⁰⁶
		5 mg/kg
		5 injections/week for 10 weeks
Male A/J mice	Experimental autoimmune myocarditis	i.p.	↓disease, ↓lymphocyte populations in heart, ↓IL-6, IFN-γ, IL-1β, and MCP-1 (CCL-2)	^126b
		10 mg/kg
		46 days
Male Wistar rats	Middle cerebral artery occlusion	i.c.v.	↓infarct size	¹⁴⁹
		50–200 ng/rat
		5 days
Male Wistar rats	Middle cerebral artery occlusion	i.c.v.	↓infarct size, ↓TNF-α	²⁰⁷
		50–200 ng/rat
		5 days
Male Wistar rats	Sodium monoiodoacetate (osteoarthritis)	Intra-arterial	↓pain, ↓rolling and adherent leukocytes, ↓joint nerve demyelination	^83b
		100–300 μg/rat
		multiple doses
Female C57BL/6 mice	Alcoholic liver disease	i.p.	↓liver damage, ↓neutrophils, ↓TNF-α, MIP-1, IFN-γ, IL-1β, and MCP-1 (CCL-2)	¹⁸⁵
		5 or 10 mg/kg
		11 days
Male and female dogs	Osteoarthritis	Oral^e	↓pain	²⁰⁸
		2 and 8 mg/kg
		every 12 h for 4 weeks
Male Wistar rats	Ulcerative tongue lesion	i.p.	↓inflammation	²⁰⁹
		5 or 10 mg/kg
		3 or 7 days
Female C57BL/6 mice	Spinal cord contusion	i.p.	↓spinal cord CD4 T cells, ↓IL-23A, IL-23R, IFN-γ, CXCL9, CLCL11, NOS2, and IL-10	¹⁸⁹
		1.5 mg/kg
		1 and 24 h after injury, on day 3, then twice/week up to 10 weeks
Male Sprague-Dawley rats	Carrageenan-induced inflammation	Oral	↓hyperalgesia	²¹⁰
		100 or 10,000 μg/kg
		once
Male Swiss mice	Haloperidol-induced inflammation	i.p	↓IL-1β and TNF-α, ↑IL-10	^97b
		60 mg/kg
		twice/day up to 21 days
Male BALB/c mice	Corneal inflammation	Topical (ophthalmic)	↓pain, ↓neutrophils	^56b
Male BALB/c mice	Corneal inflammation	3% or 5%	↓pain, ↓neutrophils	^56b
Male ICR mice	Ischemia-reperfusion injury (kidney)	i.p.	↓kidney injury, ↓TH17 cells, ↑Tregs and Treg17 cells	^152b
		10 mg/kg
		once
Female C57BL/6 and BALB/c mice	Syngeneic or allogeneic bone marrow transplant	i.p.	↓lymphocyte recovery	⁵⁷
		5 mg/kg
		every other day for 2 weeks
BALB/c mice	Ovalbumin (asthma)	i.p.	↓airway resistance; ↓IL-4, IL-5, IL-13, and eotaxin	^60b
		5 or 10 mg/kg
		three times at time of ovalbumin challenge

^{^a}

Maximum duration or frequency noted; some studies in the article might have been shorter.

^{^b}

Discussed in review.

^{^c}

Sex not stated.

^{^d}

CBD or CBD BDS (botanical drug substance).

^{^e}

CBD oil.

CBD, Cannabidiol; DNBS, dinitrobenzene sulfonic acid; iNOS, inducible nitric oxide synthase; i.n. intranasal; i.p., intraperitoneal; JNK, c-jun N-terminal kinase; LPS, lipopolysaccharide; MDSCs, myeloid-derived suppressor cells; MPO, myeloperoxidase; sRBC, sheep red blood cell; TNBS, 2,4,6-trinitrobenzene sulfonic acid; Treg, regulatory T cell.