Special Report: Psychedelics in Medicine Part 5: Psychedelic use in the long-term

Section 5: Psychedelic use in the long-term

Serious adverse reactions have not been a recognized risk through ongoing research, though some are concerned about long-term use and the time at which psychedelic drug treatment should be considered.^[1] Psychotic disorders, when they occur in a very small group of people, they are generally transient,^[2] which is a commonly-reported concern in the area of psychedelic drug research. Some of this heterogeneity can be attributed to the environment and overall well-being at time of administration, such as promoting a safe and supportive environment during treatment. This results in more positive acute effects as well as more long-lasting reductions in symptoms.^[3] In a study comparing cannabis, psilocybin, and salvinorin, cannabis resulted in a greater number of participant-reported hallucinations, though the subjective reports suggested different hallucinatory experiences compared to the acute effects of the other traditional psychedelic drugs.^[4] In terms of age at psychedelic use, there is evidence that adolescence is a particularly sensitive time in brain development. The propensity to engage in impulsive and risky behaviors is often high, and dissociative effects may occur that are not therapeutic in nature.^[5] In fact, lifetime psychotic symptoms have been associated with lifetime use of psychedelics in Germany, though this result does not account for time of use, genetic risk for psychosis, or other potential confounding. However, our understanding of the serotonergic system suggests that depletion is also a risk factor for mood and substance use disorders, such that drugs offering prolonged activity on 5-HT_2A could be advantageous for some.^[6] In sum, there is currently limited evidence of long-term risks in adults. In animal studies, however, it appears that psychedelics offer prolonged epigenetic and cognitive improvements over time.^[7] As such, despite the promising potential that psychedelic usage appears to have for medical purposes, more studies are required to fully understand long-term outcomes.

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