6.2.2 Other adverse effects
Generally, the classic psychedelics have been deemed to be relatively
low risk for adverse events,143 although there are
special populations (such as older adults, and those with cardiac
disorders) that have generally not been included in studies and deserve
particular attention to possible cardiovascular adverse events including
increased heart rate, blood pressure, and myocardial
ischemia.144 As a general concern for psychedelic
trials, reports of suicidal ideation (SI), non-suicidal self-injurious
behavior (NSSBI), and hospitalizations for severe depression have been
reported in some recent trials of psilocybin for depression as have been
noted in earlier trials of psychedelics for SUDs.145These serious psychological adverse events appear rare and may reflect
baseline risk for participants with mood disorders and/or SUDs, and it
is uncertain what additional risks that those with chronic pain may
incur. In addition, risks of hallucinogen persisting perception disorder
(HPPD) a low concern but possible concern.146 Guidance
suggests additional measurement of long term follow up for return to use
or later overdose events which would shed light on other possible risks
for psychedelics.119 Notably, rigorous reporting of
adverse events across psychedelic studies has varied and deserves
attention in future trial design.143
Other serotonergic psychedelics have cardiovascular risks, including QTc
prolongation and possible valvular disease, warranting adequate
screening and monitoring of participants with OUD, whose QTc interval
may be prolonged at baseline, and who may have underlying cardiac
disorders as a consequence of intravenous drug
use.147,148 The concurrent use of methadone, which has
relevant cardiac effects, and a psychedelic like ibogaine (also with
well documented cardiac effects) may warrant additional safety
monitoring.
Conclusion
Psychedelic-assisted interventions for chronic pain and OUD present a
promising avenue for therapeutic innovation. Although preliminary
evidence suggests potential benefits, more rigorous research is needed
to establish the safety, efficacy, and optimal protocols for
psychedelic-assisted interventions in these conditions. Future studies
should focus on carefully selected, population-specific pain- and
opioid-related outcomes, elucidating mechanisms of action, refining
treatment protocols, and addressing safety concerns. This research is
essential to ensure the responsible and evidence-based integration of
psychedelics into research settings and potentially clinical practice.
In the context of rapid attitudinal and regulatory changes regarding
psychedelics, it remains to be seen whether their therapeutic potential
for chronic pain and OUD — two of the most vexing problems of modern
healthcare — can be fully realized.