EAM-2201 acts as a full agonist with of cannabinoid receptors, CB1 and CB2. This compound was first identified in Japan in 2012 as an ingredient in synthetic cannabis smoking blends and belongs to narcotic substances, that is why was banned in some countries.

Methylcytisine (Caulophylline) is a nicotinic alkaloid found in Caulophyllum thalictroides, also known as blue cohosh. Methylcytisine is a second potentially hazardous compound identified from blue cohosh. In cultured rat embryos, N-methylcytisine from blue cohosh caused major malformations. At a concentration of 20 ppm the effects included open anterior neural tube, poor or absent eye development, and twisted tail. Higher concentrations of Methylcytisine inhibited overall growth and morphogenesis, in addition to producing similar malformations. In a separate study, Methylcytisine was also found to stimulate the ganglion cells of the cardiac vagus in frogs, paralyze the ganglia of the cardiac vagus in dogs, and produce hyperglycemia in rabbits. Some of the actions of Methylcytisine are similar to nicotine. N-Methylcytisine in blue cohosh-containing dietary supplements has been measured at concentrations ranging from 5-850 ppm. No research has been conducted on the pharmacokinetics or pharmacodynamics of blue cohosh or its constituents; therefore, the clinical significance of the experiments discussed above remains unknown. However, women anticipating a pregnancy may want to avoid using blue cohosh-containing dietary supplements until the potential in vivo teratogenic effects of this botanical are understood.

Geniposide, a key component extracted from the fruit of Gardenia jasminoides Ellis, is a major iridoid glycoside considered to be responsible for various biological effects of the herbs, and its aglycon is genipin. Gardenia is a widely used Chinese herb for the treatment of hepatic disease, inflammation disorders, contusions and brain disorders. Increasing studies have focused on the neuroprotective effect of geniposide in brain diseases, especially neurodegenerative disorders. Its protective effect from memory impairment and the normalization of objection recognition has been shown in animal behavioral experiments. Using a high-throughput screen for GLP-1R agonists, geniposide was identified as an agonist for GLP-1R. It has been shown that the activation of GLP-1R by geniposide induces neurotrophic and neuroprotective effects in cells. Geniposide exerted anti-inflammatory effects by interfering with the expression of P2Y14 receptor, which subsequently inhibits the downstream ERK1/2 signaling pathways and the release of the pro-inflammatory cytokines IL-8, MCP-1, IL-1β.

N,N-dimethylglycine or dimethylglycine (DMG) is an amino acid derivative found in the cells of all plants and animals and can be obtained in the diet in small amounts from grains and meat. The human body produces DMG when metabolizing choline into glycine. DMG has been found acting at glycine binding site of the N-methyl-d-aspartate receptor (NMDAR). DMG has had wide acceptance as a nonfuel nutrient; presumably it enhances oxygen utilization by tissue and complexes free radicals. There were published studies, which have shown little to no difference between DMG treatment and placebo in autism spectrum disorders and the same no effect was observed in case of investigated DMG for epilepsy. This compound was also suggested to use to improve the athletic performance enhancer, but this usage was ineffective as well.

Yangonin is a natural kavalactone found in the kava plant. Yangonin has been shown to possess binding affinity for the cannabinoid receptor CB1, where it behaves as an agonist. Yangonin also inhibits anchorage-dependent and independent growth of bladder cancer cell lines through induction of autophagic cell death. Yangonin displays marked in vitro toxicity on human hepatocytes with approximately 40% reduction in viability based on an ethidium bromide assay and FDA advises against the use of kava in food due to the potential risk of severe liver damage.

10-Hydroxy-2-decenoic acid, a natural fatty acid that has been extracted from royal jelly obtained from honeybees (Apis mellifera) and exhibits estrogenic action. 10-hydroxy-2-decenoic(10-HDA)dose-dependently inhibited the formation of the gastric ulcer induced by stress, pyloric ligation, and indomethacin selectively in rats. 10-HDA also accelerated the healing of gastric ulcer induced by acetic acid, by which the gastric acid output was decreased in a dose-dependent manner. A mechanism putatively linked to 10-HDA anti-inflammatory effect is the inhibition of LPS-induced NF-kB activation observed in the murine macrophage cell line RAW264. 10-HDA and 4-hydroperoxy-2-decenoic acid ethyl ester have been shown to inhibit histone deacetylase activity, thereby enhancing the expression of extracellular SOD release by leukemia THP-1 cells, and suggesting therapeutic potential against atherosclerosis. Various immunomodulatory activities have been reported for 10-HDA, including reduced T cell proliferation, inhibition of interleukin-12 production by spleen dendritic cells, and blocks of LPS- and IFN-b-induced NO production in macrophages. 10-HDA has been shown to increase collagen synthesis and production of the collagen promoting factor, transforming growth factor b1, in human skin fibroblasts. Such an effect is thought to mediate royal jelly skin protection against UVB-induced photoaging. 10-HDA and 10-hydroxydecanoic acid have been shown to act as potent agonists of the human TRPA1 and TRPV1 receptors. 10-HDA has stimulated neuron differentiation from rat embryo neural stem cells, possibly acting like the omega-3 docosahexaenoic acid, an essential diet component that is known to promote neurogenesis in the central nervous system.

Dimaprit (S-[3-(N,N-dimethylamino)propyl]isothiourea) has been shown to be a highly specific histamine H2-receptor agonist.