Nature
January 1, 2021
Lindsay P Cameron, Robert J Tombari, Ju Lu et al.
468 citations
Ibogaine, a psychedelic alkaloid, shows anti-addictive effects in humans and animals but has safety issues including toxicity and heart arrhythmias. Researchers engineered tabernanthalog, a water-soluble, non-hallucinogenic, non-toxic analogue made in a single step. In rodents, tabernanthalog promoted structural neural plasticity, reduced alcohol- and heroin-seeking behavior, and produced antidepressant-like effects. This demonstrates that careful chemical design can create safer, non-hallucinogenic variants of psychedelic compounds with therapeutic potential.
Neuroscience insights
January 1, 2021
Jamie Peters, David E Olson
38 citations
Addiction arises from maladaptive neuroplasticity that strengthens reward pathways driving compulsive drug seeking while weakening circuits for executive control. Psychedelics show promise for treating addiction, often attributed to insights gained during hallucinations, but they are also potent psychoplastogens that rapidly rewire the adult brain. Non-hallucinogenic psychoplastogens, such as tabernanthalog (TBG), have anti-addictive properties in preclinical models for alcohol and opioid addiction, suggesting hallucinations may not be necessary for therapeutic effects if pathological neural circuitry is repaired. This review discusses implications for addiction treatments and next steps for advancing TBG and related compounds.
Psychedelic medicine (New Rochelle, N.Y.)
June 1, 2023
Jasper A Heinsbroek, Giuseppe Giannotti, Joel Bonilla et al.
26 citations
Tabernanthalog (TBG), a novel analogue of ibogaine and 5-methoxy-N,N-dimethyltryptamine, lacks classical psychedelic effects and cardiac arrhythmogenic risk. In a polydrug model of heroin and alcohol co-use in rats, TBG reduced motivation for both substances in a progressive ratio test, where the number of lever presses required for a reward increased exponentially. The study used a two-bottle binge protocol for alcohol exposure, followed by self-administration training for intravenous heroin or oral alcohol, and then sessions with both substances. TBG's efficacy was preserved in animals with a history of heroin and alcohol polydrug use.
Neuropharmacology
September 26, 2024
J. Alfred Bonilla, Giuseppe Giannotti, Nathaniel P. Kregar et al.
12 citations
In a rat model of polydrug use where animals self-administered both intravenous heroin and oral alcohol, the psychedelic compound DOI (0.4 mg/kg) reduced motivation for heroin, measured as the break point in a progressive ratio test. This effect was blocked by a 5-HT2A receptor antagonist but not by a 5-HT2C antagonist, indicating the effect is mediated by 5-HT2A receptors. DOI did not affect motivation for alcohol. The findings suggest that psychedelic drugs acting as 5-HT2A agonists may reduce opioid motivation in individuals with opioid and alcohol co-use.