TABLE 2.

Antipsychotic potential of phytochemicals in clinical studies.

Chemical Class	Phytochemical	Source	Assessments	Dose	Study Design	Mechanism	Result	References
Alkaloids	Apomorphine	Nymphea caerulea	Interview using NHSI (new haven schizophrenia index)	1.5 to 6 mg	Randomized double blind placebo study	Potent effect on presynaptic dopamine receptors in addition to its postsynaptic stimulation	Decrease in psychotic symptoms in chronic patients	Smith et al. (1977); Fletcher, Frith et al. (1996)
	Reserpine	Rauolfia serpentina	Seven-point behavioral rating scale	1–8 mg/day	Controlled study of 8 months	Depressor of hypothalamus and facilitator of synaptic transmission	Marked improvement in behavior occurred	Cowden et al. (1955)
	Nicotine	Nicotiana tabacum	Profile of mood states (POMS) and continuous performance test (CPT)	7 mg/day	N/A	Alpha 7 nicotinic receptor agonist	Attentional function is increased	(Levin, Conners, Silva, Hinton, Meck, March and Rose 1998)
Amino acid and derivatives	Glycine	Glycine max	PANSS and Scale for assessing Negative Symptoms (SANS)	0.14 to 0.8 g/kg/day	Open label trial	Potentiate NMDA transmission	Improvement in negative symptoms	Leiderman et al. (1996)
	Sarcosine	Arachis hypogaea	Positive and Negative Syndrome Scale total score	1–2 g/day for six weeks add on therapy	Double blind randomized clinical trial	Glycine 1 transport inhibitor, increases N-methyl-d-aspartate transmission	Reduced positive and negative syndromes in anti-psychotic naïve patients	Lane et al. (2008)
Cannabinoids	Tetrahydrocannabinol	Cannabis ruderalis	Clinical global impression, brief psychiatric rating scale	2.5 to 10 mg twice a day	Clinical case study	Affecting endocannabinoid receptors	Refractory schizophrenia symptoms improved	Schwarcz et al. (2009)
	Cannabidiol	Cannabis sativa	Positive and negative symptoms, Global assessment of functioning scale	1000 mg/day for six weeks	Double blind randomized clinical trial	As adjunct therapy	Reduced positive symptoms and improved cognitive performance	Philip McGuirePsych. et al. (2018)
Flavonoids/ Polyphenols	Luteolin	Salvia rosmarinus	N/A	N/A	N/A	Modifier of NMDA function	Schizophrenic symptoms decreased	Hannan et al. (2021)
	Apigenin	Perilla fruitiscenscens	N/A	N/A	N/A	Restore function of NMDA receptor by modulating hSKCa3 channel	Schizophrenic symptoms decreased	Hannan et al. (2021)
Phenolic acid and derivatives	Sodium benzoate	Styrax benzoin	Assessment of positive and negative symptoms, and clinical global impression in treatment refractory schizophrenia	0.5 g twice a day for 12 weeks	Double blind randomized clinical trial	Adjunctive use	Lack of efficacy in patients with early psychosis	Scott et al. (2020)
	Sodium benzoate	Styrax benzoin	Clinical Global Impression (CGI), assessment of negative symptoms	1 g/day for six weeks add-on therapy	Double blind randomized clinical trial	d-amino acid oxidase inhibitor	Improvement of clinical symptoms and recognition	Lane et al. (2013)
Polyphenols	Resveratrol	Vitis vinifera	positive and negative symptoms scale and extrapyramidal symptoms scale	200 mg/day for eight weeks add on therapy	Double blind randomized clinical trial		Managed negative symptoms and increased efficacy of risperidone	Samaei et al. (2020)
Sesquiterpenoids	Caryophyllene	Cannabis sativa	N/A	25 to about 100 mg add-on therapy	Clinical trials (application N° EP13763464.8A)	CB2-selective phyto-cannabinoid	Might improve schizophrenia symptoms	Anavi-goffer and Gertsch (2015)