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Brian D Kangas

Jerry and Phyllis Rappaport Center of Excellence in Basic Neuroscience Research, Harvard Medical School McLean Hospital, Belmont, MA 02478.

5 papers in the library · 48 citations · publishing 2024-2026

Papers

Molecular design of a therapeutic LSD analogue with reduced hallucinogenic potential

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.

Environmental determinants of ketamine's prohedonic and antianhedonic efficacy: Persistence of enhanced reward responsiveness is modulated by chronic stress.

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.

A Multimodal Preclinical Assessment of MDMA in Female and Male Rats: Prohedonic, Cognition Disruptive, and Prosocial Effects.

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.

Ketamine Improves Anhedonic Phenotypes Across Species: Translational Evidence From the Probabilistic Reward Task.

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.

Chronic Δ9-tetrahydrocannabinol exposure during adolescence is associated with persistent behavioural tolerance in adult nonhuman primates.

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.