Psychedelic substances may offer therapeutic benefits for psychiatric disorders by acting through specific cellular mechanisms. This review describes how these compounds primarily signal through the 5-HT2A receptor and promote neural plasticity via the TrkB-BDNF pathway. It also covers their effects on other receptors and pathways, as well as their potential anti-inflammatory properties. The work highlights a promising direction for developing new mental health treatments.
Methylone, a synthetic cathinone and beta-keto analogue of MDMA, produces acute subjective and physiological effects similar to MDMA but less intense. In an observational-naturalistic study of 14 healthy poly-drug users who self-administered oral doses (methylone 100-300 mg, mean 187.5 mg; MDMA 75-100 mg, mean 87.5 mg), methylone showed a prototypical psychostimulant and empathogenic profile. Oral fluid concentrations of both substances peaked at 2 hours, with MDMA levels matching those from controlled studies. The findings indicate that methylone's abuse potential is comparable to MDMA's in recreational users.
Synthetic cannabinoid UR-144, monitored by the EU Early Warning System since 2012 for severe adverse effects, shows a similar cardiovascular profile to delta-9-tetrahydrocannabinol (THC) but with less intense subjective effects. In an observational study, 16 volunteers smoked joints containing either UR-144 (1 or 1.5 mg) or cannabis (10 or 20 mg THC). Both substances significantly increased systolic and diastolic blood pressure and heart rate. UR-144 produced lower scores on visual analog scales for stimulant-like and high effects compared to cannabis, and no hallucinogenic effects were observed. UR-144 was detectable in oral fluid, peaking at 20 minutes after smoking, offering a non-invasive biomarker of consumption. These preliminary findings require confirmation in larger samples.