Classic serotonergic psychedelics such as psilocybin, LSD, and ayahuasca may improve mood and reduce depressive symptoms more than placebo, with effects appearing within hours and lasting up to 60 days. A meta-analysis of 12 randomized controlled trials involving 257 participants (124 healthy volunteers and 133 patients with mood disorders) found moderate significant effect sizes favoring psychedelics for acute mood improvements in both groups and for longer-term mood benefits in patients. For patients with mood disorders, significant reductions in depressive symptoms were seen acutely, at 2–7 days, and at 16–60 days after treatment. Although unblinding and expectancy are concerns, the strength, speed, and durability of effects support further placebo-controlled trials.
Acute doses of cannabidiol (CBD) reduce anxiety in both animals and humans without causing anxiety at higher doses, while tetrahydrocannabinol (THC) commonly produces anxiety, especially at higher doses. Epidemiological studies support an anxiolytic effect from CBD, THC, or whole-plant cannabis, but human clinical studies show THC often triggers anxiogenic responses. Cannabinoid therapies containing primarily CBD may be more suitable for people with pre-existing anxiety or as an adjunct for managing anxiety or stress-related disorders. Further research is needed on other cannabis constituents like terpenes, and more clinical trials involving patients with anxiety disorders are warranted.