In a small clinical trial with 16 adults suffering from treatment-resistant depression, an inhaled form of the psychedelic drug 5-MeO-DMT (GH001) was well tolerated and produced rapid antidepressant effects. An individualized dosing regimen of up to three increasing doses within a single day led to 87.5% of patients achieving remission (a depression score of 10 or less on the MADRS scale) by day 7, compared to 50% and 25% for single doses of 12 mg and 18 mg, respectively. Remission occurred as early as two hours after dosing for some patients. The findings suggest that individualized dosing may be more effective than a single dose.
Cannabis use is considered a contributory cause of schizophrenia and psychotic illness, but only a small proportion of users develop psychosis. The amount, duration, and strength of cannabis consumption, as well as age at first exposure, partly explain this. Genetic factors likely play a role in both short- and long-term effects on psychosis. This review discusses studies using genetic, epidemiological, experimental, and observational techniques to investigate gene-environment correlation and interaction within the cannabis-psychosis association. Evidence suggests that mechanisms of gene-environment interaction underlie the link, with multiple genetic variations and other environmental factors (e.g., stress) interacting with cannabis to increase psychosis risk. Further research on higher-order interactions is needed.
Psychotic experiences (like mild hallucinations or delusions) are common and often temporary in the general population. This study tested whether they become abnormally persistent when combined with environmental factors such as cannabis use, childhood trauma, and urban living. Using two large Dutch and German population samples, the authors found that persistence rates were low overall (26% and 31%) but increased progressively with more environmental exposures. Among those exposed to both environmental risks and baseline psychotic experiences, 21%-83% (Dutch sample) and 29%-51% (German sample) had persistent symptoms due to the synergistic interaction of these factors. The authors argue that environmental risks combine additively and synergistically with non-clinical psychotic experiences to drive persistence and eventual need for care.