Proceedings of the National Academy of Sciences
April 14, 2025
Jeremy R Tuck, Lee E. Dunlap, Yara A Khatib et al.
32 citations
A newly designed compound, (+)-JRT, structurally similar to LSD but with reduced hallucinogenic effects, promotes the growth of dendritic spines in the cortex—a process that is diminished in neuropsychiatric diseases such as depression, addiction, and schizophrenia. In behavioral tests, (+)-JRT showed antidepressant-like and cognition-enhancing effects without worsening signs related to psychosis. This suggests that nonhallucinogenic compounds that promote neuroplasticity could be safer alternatives to psychedelics for treating conditions where psychedelics pose risks.
The Journal of pharmacology and experimental therapeutics
May 1, 2025
Amaya R Jenkins, Daniela B Radl, Thomas J Kornecook et al.
8 citations
Ketamine produces short-lived increases in reward responsiveness in rats under nonstressful conditions, but under ongoing chronic stress it rescues blunted reward responsiveness for nearly one week. These findings highlight the role of environmental context in ketamine's effects on reward processing and suggest its antianhedonic action may contribute to its antidepressant efficacy.
Psychedelic medicine (New Rochelle, N.Y.)
June 1, 2024
Abshir S Adam, Kayleigh S. Lamalfa, Yasaman Razavi et al.
6 citations
MDMA produces dose-dependent increases in reward responsivity, a measure of anhedonia, in rats, along with dose-dependent deficits in attention and short-term memory, and increases in prosocial interaction in male but not female rats. The desirable prohedonic effects and undesirable cognitive disruptions do not persist beyond 24 hours. These results characterize MDMA as a promising prohedonic treatment despite short-lived cognitive impairment following acute administration.
Biological Psychiatry Global Open Science
May 1, 2026
Mario Bogdanov, Jason N Scott, Shiba M Esfand et al.
1 citation
A single low dose of ketamine improves the ability to learn from rewards in both people with treatment-resistant depression and stressed rats, using nearly identical tasks. Twenty-four hours after receiving ketamine, individuals with treatment-resistant depression and chronically stressed rats showed a stronger tendency to choose the more frequently rewarded option, matching the performance of healthy controls. This effect was most pronounced in people with more severe anhedonia at the start. Ketamine did not affect general task accuracy, indicating it selectively boosts reward learning rather than overall performance. These findings point to a shared behavioral mechanism by which ketamine alleviates anhedonia, with potential implications for treating anhedonia in depression and related conditions.
British Journal of Pharmacology
November 1, 2025
Yasaman Razavi, Stephen J Kohut, Jack Bergman et al.
1 citation
Adolescent monkeys exposed daily to the cannabis compound Δ9-THC for six months, then tested about a year later as adults on a touchscreen attention task, required higher acute doses of Δ9-THC to impair their performance compared with animals that had not been exposed during adolescence. The impairment itself was dose-related and occurred whether the drug was given by injection or orally, though potency and timing differed. These results suggest that heavy cannabis use during adolescence can produce a lasting tolerance that persists into adulthood, even after a long period of abstinence.
medRxiv Preprint Server
June 2, 2025
Mario Bogdanov, Jason N Scott, Shiba M Esfand et al.
1 citation
preprint
A single, subanesthetic dose of ketamine improved reward responsiveness in both humans with treatment-resistant depression and chronically-stressed rats, measured using functionally identical tasks. The finding suggests that ketamine's rapid antidepressant effects may involve enhancing reward processing, a core feature of anhedonia. The work provides translational evidence linking preclinical and clinical observations, though the mechanisms remain unclear.
July 9, 2018
Chu Hsien Lim, Brian D Kangas, Jack Bergman
1 citation
Cancer patients face elevated rates of depression and anxiety, often leading to worse healthcare outcomes. Given limited treatment options, interest has grown in using psychedelics like psilocybin to manage these complications. Recent studies have shown the potential of psilocybin to alleviate depression and anxiety in cancer patients.
Neuropsychopharmacology
July 10, 2026
Christopher W. Thomas, Kayleigh S. Lamalfa, Tobias P. Whelan et al.
Psilocybin and ketamine acutely increased reward responsiveness in rats, and the effect persisted 24 hours after dosing. The increase from psilocybin, but not ketamine, was blocked by a 5-HT2A receptor antagonist. Other psychedelics, DMT and DOI, also acutely increased reward responsiveness but the effect did not last 24 hours. The non-psychedelic 5-HT2A agonist lisuride and the SSRI fluoxetine had no positive effects. These results suggest psychedelics can produce acute and enduring increases in reward responsiveness, partly through the 5-HT2A receptor, though the time course varies and clinical implications require further validation.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
October 1, 2025
Andrew Jin Soo Byun, Harshawardhan U Deshpande, Jessi Stover et al.
Chronic delta-9-tetrahydrocannabinol (THC) exposure during adolescence alters functional connectivity between the default mode and central executive networks in the adult brain in a dose-dependent manner. In squirrel monkeys given daily low (0.32 mg/kg) or high (3.2 mg/kg) THC injections for six months during adolescence, only the low dose increased connectivity between these networks during the exposure period, an effect that reversed after discontinuation. The high dose and vehicle controls showed no such change. The central executive network appeared to drive this effect. The findings suggest that adolescent THC exposure can produce non-linear, dose-dependent disruptions in large-scale brain networks.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
February 1, 2025
Brian D Kangas, Harshawardhan U Deshpande, Sarah L Withey et al.
Chronic exposure to THC during adolescence in squirrel monkeys produces long-lasting changes in brain functional connectivity and motivation that persist into adulthood. Daily treatment with either a low (0.32 mg/kg) or high dose (3.2 mg/kg) of THC for six months during adolescence led to persistent alterations in connectivity of the medial orbitofrontal cortex, caudate, and ventral striatum. In economic demand tests, THC-treated subjects showed dosage-dependent disruption in reward sensitivity and motivation, unlike vehicle-treated subjects who displayed the expected inverse relationship between reward magnitude and effort. The findings indicate that adolescent THC exposure causes enduring neurocognitive abnormalities in reward processing.