Engineering Safer Psychedelics for Treating Addiction.

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.

Study at a glance

Abstract

Addiction is best described as a disorder of maladaptive neuroplasticity involving the simultaneous strengthening of reward circuitry that drives compulsive drug seeking and weakening of circuits involved in executive control over harmful behaviors. Psychedelics have shown great promise for treating addiction, with many people attributing their therapeutic effects to insights gained while under the influence of the drug. However, psychedelics are also potent psychoplastogens-molecules capable of rapidly re-wiring the adult brain. The advent of non-hallucinogenic psychoplastogens with anti-addictive properties raises the intriguing possibility that hallucinations might not be necessary for all therapeutic effects of psychedelic-based medicines, so long as the underlying pathological neural circuitry can be remedied. One of these non-hallucinogenic psychoplastogens, tabernanthalog (TBG), appears to have long-lasting therapeutic effects in preclinical models relevant to alcohol and opioid addiction. Here, we discuss the implications of these results for the development of addiction treatments, as well as the next steps for advancing TBG and related non-hallucinogenic psychoplastogens as addiction therapeutics.