Table 1.

Anti-inflammatory properties of alternative antidepressant treatments.

Drug Classification	Mood/Affect	Inflammation	Sources
Ketamine/NMDA receptor antagonists	- rapid onset (30 min) of antidepressant effects, especially in treatment resistant depression - decreased rumination, depressive behaviors, and depression scores - Antidepressant effects persist for up to 7 days	- Decreased pro-inflammatory cytokines (i.e., TNF-α) that are correlated with decreased depression	Human •Cathomas et al. (2022) •Chen et al. (2018) •Chen et al. (2021) •Lehmann et al. (2016) •Liebrenz et al. (2009) •Su et al. (2017) •Zarate et al. (2006) •Zhan et al. (2020) Animal •Chang et al. (2018) •Wang et al. (2015) •Zhao et al. (2020)
Cannabis/Cannabinoid	- THC, CBD, and HU-580 show antidepressant-like effects in rodent behavioral tests - UCS decreases eCB signalling - FAAH enzyme inhibition leads to anti-depressant effects	- Decreased inflammatory cytokines (e.g., IL-6, TNF-α, IFN-ß) - Decreased PGE2, COX activity, oxygen-derived free radicals, and nitric oxide - Chronic stress induces inflammation which is rescued by cannabinoid treatment	Human •Karoly et al. (2018) •Motwani et al. (2018) •Morissette et al., 2021 Animal •Hill et al. (2005) •Haj-Dahmane and Shen (2014) •Bambico et al. (2016) •Bambico et al., 2010a, Bambico et al., 2010b •Elbatsh et al. (2012) •Costa et al. (2004) •Abohalaka et al. (2020) •Hen-Shoval et al. (2018) •Verrico et al. (2020) •Yekhtin et al. (2022)
Psychedelics	- Decreased stress and anxiety-related behaviors - Rapid and long-term antidepressant effects in MDD lasting up to 6 months	- Decreased CRP that correlates with decreased depression - 5-MeO-DsMT increased cortisol and decreased IL-6	Human •Galvão-Coelho et al. (2020) •Uthaug et al. (2020) •Griffiths et al. (2016) •Davis et al. (2021) •Barrett et al. (2020) Animal •Yu et al. (2008) •Flanagan et al. (2021)

Note: Acronyms: UCS – unpredictable chronic stress, eCB – endocannabinoids, FAAH - Fatty acid amide hydrolase, TNF-α - Tumor necrosis factor alpha, IFN-ß – Tumor necrosis factor beta, PGE2 - Prostaglandin E2, COX – cyclooxygenase, CRP – C-reactive protein, 5-MeO-DMT - 5-methoxy-N,N-dimethyltryptamine, IL-6 – Interleukin-6, HU-580 – cannabidiolic acid methyl ester, MDD – major depressive disorder.