Anhedonia, the blunted responsiveness to previously rewarding stimuli, is a core symptom of several psychiatric disorders. Ketamine and psilocybin have shown promising evidence in ameliorating anhedonic symptoms in clinical trials. The Probabilistic Reward Task (PRT) was developed to objectively quantify reward responsiveness in clinical populations and laboratory animals. Here, the PRT was...
Ketamine is increasingly used as a therapeutic option for treatment-resistant depression (TRD) due to its rapid antidepressant properties; however, the mechanisms underlying these effects remain elusive. Preclinical evidence suggests ketamine acts on neural pathways implicated in reward processing, but translational efforts have proven challenging due to a lack of paradigms allowing for...
Legalisation of Cannabis use has led to considerable increases in the availability and potency of Cannabis products, as well as evolving patterns in methods of their consumption. Adolescent Cannabis use has increased, which can impair cognitive function during this critical developmental stage. The persistence of such effects into adulthood, however, is unclear. The present study examined...
NeuropsychopharmacologyOctober 1, 2025Andrew Jin Soo Byun, Harshawardhan U Deshpande, Jessi Stover et al.
Adolescent cannabinoid exposure has been implicated in enduring modifications to adult brain circuitry; however, well-controlled, systematic analyses investigating dose-dependent effects of chronic delta-9-tetrahydrocannabinol (THC) exposure on brain connectivity are lacking. It is hypothesized that large-scale intrinsic networks, such as default mode (DMN), central executive (CEN), and...
Ketamine, a dissociative anesthetic with well documented abuse liability, can also provide rapid-onset and persistent antidepressant effects and is currently used for the management of treatment-resistant depression. Although the precise neurobiological mechanisms underlying its antidepressant actions are not fully determined, a critical feature of ketamine's clinical efficacy may be its...
Decreased dendritic spine density in the cortex is a key pathological feature of neuropsychiatric diseases including depression, addiction, and schizophrenia (SCZ). Psychedelics possess a remarkable ability to promote cortical neuron growth and increase spine density; however, these compounds are contraindicated for patients with SCZ or a family history of psychosis. Here, we report the...
Although chronic cannabis use during adolescence can alter brain function and impair complex behavioral processes, it is unclear whether such deficits persist into adulthood. Using a coordinated awake neuroimaging and behavioral approach in nonhuman primates, we addressed this issue by examining the impact of chronic adolescent exposure to Δ9-tetrahydrocannabinol (THC) on brain functional...
Psychedelic MedicineJune 1, 2024Abshir S Adam, Kayleigh S. Lamalfa, Yasaman Razavi et al.6 citations
Frontline antidepressants such as selective serotonin reuptake inhibitors (SSRIs) leave many patients with unmet treatment needs. Moreover, even when SSRIs reduce depressive symptoms, anhedonia, the loss of pleasure to previously rewarding activities, often remains unabated. This state of affairs is disheartening and calls for the development of medications to more directly treat anhedonia. The...
Cancer patients experience a higher rate of depression and anxiety which can result in negative healthcare outcomes. With the limited treatment options available, there has been an interest in using psychedelics such as psilocybin to manage such complications. Recently, two studies demonstrated the
The primary psychoactive ingredient of marijuana, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), has medicinal value but also produces unwanted deleterious effects on cognitive function, promoting the search for improved cannabinergic therapeutics. The present studies used a battery of touchscreen procedures in squirrel monkeys to compare the effects of different types of cannabinergic drugs on several...
In the reward circuitry of the brain, α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates...
Cannabinoid receptor 1 (CB(1)) inverse agonists (e.g., rimonabant) have been reported to produce adverse effects including nausea, emesis, and anhedonia that limit their clinical applications. Recent laboratory studies suggest that the effects of CB(1) neutral antagonists differ from those of such inverse agonists, raising the possibility of improved clinical utility. However, little is known...