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Effects of psychedelics on opioid use disorder: a scoping review of preclinical studies

Alejandra Pulido-Saavedra1,2, Henrique Nunes Pereira Oliva1,2, Tiago Paiva Prudente3

  • 1Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, CT, 06511, USA.

Cellular and Molecular Life Sciences : CMLS
|January 20, 2025
PubMed

Insights

Psychedelics like ibogaine and ketamine show promise in preclinical studies for treating opioid use disorder (OUD) by reducing self-administration and withdrawal. Further research is needed to explore broader psychedelic options and their safety profiles for OUD treatment.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Public Health

Background:

  • The opioid crisis necessitates novel treatments beyond existing medications for opioid use disorder (OUD).
  • Preliminary evidence suggests psychedelics may offer therapeutic benefits for OUD, but robust clinical data is limited.
  • Existing treatments for OUD have limitations, driving the search for innovative therapeutic strategies.

Purpose of the Study:

  • To systematically review preclinical in vivo studies on psychedelics for opioid use disorder (OUD).
  • To bridge the gap between preclinical findings and potential clinical applications of psychedelics in OUD treatment.
  • To identify promising psychedelic compounds and areas for future research in OUD therapy.

Main Methods:

  • Conducted a systematic literature search across major databases (MEDLINE, Embase, Scopus, Web of Science) following PRISMA-ScR guidelines.
  • Included preclinical in vivo studies of psychedelics and opioids in animal models, excluding pain studies and uncontrolled trials.
  • Analyzed 40 studies investigating classic and non-classic psychedelics for their effects on opioid self-administration, withdrawal, and conditioned place preference.

Main Results:

  • Most studies indicated that 18-methoxycoronaridine (18-MC), ibogaine, noribogaine, and ketamine reduced opioid self-administration and withdrawal symptoms.
  • Seven studies reported no significant improvement over control groups for certain psychedelics, including DOM, ibogaine, 18-MC, and ketamine.
  • Methodological quality assessment revealed that most studies had unclear quality, and preclinical research heavily favors iboga derivatives, which may pose cardiovascular risks.

Conclusions:

  • Preclinical evidence supports further translational studies investigating psychedelics as innovative treatments for opioid use disorder (OUD).
  • Future clinical research should broaden the scope beyond iboga derivatives to include other psychedelics.
  • Further investigation is required into the mechanisms of action, safety profiles, optimal dosages, and administration frequencies of psychedelics for OUD.
Keywords:
Conditioned place preferenceDependenceOpioid use disorderPsychedelicsSelf-administrationWithdrawal

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