The biphasic effect reported in animal studies, with low doses reducing anxiety and high doses producing anxiogenic-like and antidepressant-like effects [69,70,71,72] are also seen in humans. THC has demonstrated biphasic, dose-dependent effects on anxiety in healthy adults [173,174,175,176,177,178]. Neuroimaging data have also confirmed that THC can both increase [175] and decrease [174] emotional arousal/processing of negative stimuli at specific doses [178]. Certain THC doses globally induced anxiogenic effects in healthy individuals, although in this study half of the subjects were recreational users of cannabis [108,179]. However, due to the credible harmful effects over the long-term, such as addictive potential and the induction of anxiety and depression, multiple meta-analyses and reviews warn against the use of high doses of pure THC or cannabis-based preparations containing THC for long periods of time [108,128].
