Oral ketamine shows potential as an antidepressant for unipolar and bipolar depression, based on a systematic review of 22 studies involving 2336 patients. All included studies reported significant improvement after ketamine administration, and it was well tolerated without serious adverse events. However, the review identified important limitations, including a small number of randomized clinical trials (only four) and a high risk of bias in those trials due to analysis methods and adverse events monitoring. Ketamine dosages ranged from 0.5 to 1.25 mg/kg, with administration frequency from daily to monthly. Further research with larger samples and longer follow-up is needed to determine its antisuicidal effect and efficacy in treatment-resistant depression.
Exposure to cannabis increases the risk for psychoses ranging from transient psychotic states to chronic recurrent psychosis. Greater dose and earlier age of exposure raise the risk. For some psychosis outcomes, evidence supports some causality criteria, but reverse causality and confounders cannot be ruled out. Cannabis is neither necessary nor sufficient to cause psychosis; it is likely one of multiple causal components. In those with established psychosis, cannabis negatively affects the illness course and expression. Emerging evidence suggests alterations in the endocannabinoid system in psychotic disorders. Delaying or eliminating cannabis exposure could potentially reduce psychosis rates, especially in high-risk individuals.