Cellular and molecular life sciences : CMLS
January 21, 2025
Alejandra Pulido-Saavedra, Henrique Nunes Pereira Oliva, Tiago Paiva Prudente et al.
5 citations
The opioid crisis has driven a search for new treatments for opioid use disorder (OUD). A systematic review of 40 preclinical animal studies found that the psychedelic compounds 18-methoxycoronaridine (18-MC), ibogaine, noribogaine, and ketamine generally reduced opioid self-administration, eased withdrawal symptoms, and altered conditioned place preference. However, seven studies showed no improvement over controls. Most research has focused on iboga derivatives, which appear effective but carry higher cardiovascular risk than other psychedelics. The review calls for more translational and clinical studies that test a broader range of psychedelic agents and explore mechanisms, safety, dosing, and treatment frequency.
Psychiatry research
June 1, 2025
Jeremy Weleff, Alejandra Pulido-Saavedra, Ardavan Mohammad Aghaei et al.
4 citations
A systematic review of clinical studies on psychedelics for opioid use disorder found few completed trials using serotonergic psychedelics; most investigated ibogaine or ketamine. The evidence is limited by weak study designs focused on opioid withdrawal, few double-blind or placebo-controlled trials, and considerable methodological heterogeneity that makes comparisons across compounds difficult. Most studies had a high risk of bias, mainly due to lack of randomization, blinding, and blinded outcome assessment. The review outlines these limitations and steps to improve the quality of future research in this area.
Expert opinion on pharmacotherapy
February 1, 2025
Alejandra Pulido-Saavedra, Anna Borelli, Razi Kitaneh et al.
Substance use disorders remain a public health challenge; few have FDA-approved treatments, and those that do suffer from high dropout rates. This narrative review examined clinical evidence for non-psychedelic medications that primarily target the 5-HT2A receptor. Results on craving and abstinence were mixed, with some positive effects but no consistent pattern. Comparing these findings with those for psychedelic agents (which are typically 5-HT2A agonists) suggests that mixed results are not unique to non-psychedelics. Because most non-psychedelic agents reviewed are 5-HT2A antagonists, while psychedelic agonists show more uniformly positive outcomes, the authors propose that 5-HT2A receptor agonists are a promising avenue for treating substance use disorders, possibly by addressing a common underlying chronic hypodopaminergic state.