Psychopharmacology
April 24, 2026
Melissa L. Perreault, T. Ryan Gregory, Andrew Maxwell Phineas Jones
Whole plants and mushrooms have been used in traditional medicine for millennia, and their use is growing in modern Western societies. Cannabis and psilocybin are prominent examples, driven by greater accessibility, socioeconomic and environmental stress, and evidence of therapeutic value. The medicinal cannabis market was valued at over $21 billion in 2025, projected to reach $116 billion by 2033. The global psychedelic mushroom market is predicted to double to $3.3 billion by 2031, though the medicinal portion is unclear. Other examples include ayahuasca, lion's mane mushrooms, and products used recreationally or for health enhancement.
Psychopharmacology
April 23, 2026
Stefani Kalli, Alina Davletova, Lenka Seillier et al.
Rats treated with phencyclidine (PCP) to model schizophrenia's negative symptoms showed reduced overall social interaction compared to controls, but the deficit was selective: some behaviors (e.g., Following) were impaired while others were not. A detailed analysis of 42 behaviors revealed that PCP-treated rats also displayed a persistent attentional bias toward the inanimate environment during both habituation and social exposure, suggesting their attention was displaced away from other rats. This multidimensional behavioral approach uncovers a more nuanced phenotype than simple total interaction time, indicating altered attentional allocation as a possible mechanism underlying social withdrawal in this model.
Psychopharmacology
April 14, 2026
Guilherme Lodetti, Antonio Inserra, Henrique Redivo et al.
A single exposure to ayahuasca reversed behavioral and biochemical changes caused by 14 days of unpredictable chronic stress in adult zebrafish. Stressed fish showed impaired sociability, anxiety-like behavior, hyperactivity, elevated whole-body cortisol, and reduced whole-brain BDNF. Ayahuasca restored sociability, reduced anxiety-like behavior and hyperactivity, normalized cortisol levels, and increased BDNF. These findings suggest ayahuasca can reverse stress-induced behavioral and neuroendocrine alterations, supporting further clinical studies for chronic stress.
Psychopharmacology
March 4, 2026
Ava M. Mac, Srinivasu Kallakuri, Alixandria T. Mascarin et al.
Repeated low doses of MDMA (2.5 mg/kg) caused mild anxiety-like behavior in rats one day after exposure, but this effect was confounded by reduced movement and did not persist at 15 days. Higher doses (5 mg/kg) did not produce anxiety-like behavior. Sucrose preference, a measure of anhedonia, increased over time and was unaffected by MDMA or sex. Brain analysis showed reduced serotonin levels in the nucleus accumbens one day after both MDMA doses, but not in the prefrontal cortex or dorsal hippocampus. These transient effects suggest that low-dose MDMA used clinically may be tolerated without limiting therapeutic benefit.
Psychopharmacology
March 1, 2026
Taren Mieran, Andrew Hill, Mark S Horswill et al.
Medicinal cannabis users who consumed THC oil did not show a decline in their actual ability to detect hazards while driving, but their confidence in that ability dropped. There was no link between how well they thought they performed and how well they actually performed, regardless of THC consumption. After taking THC, users drove slower and kept longer following distances, suggesting they compensated for perceived impairment. Gap acceptance and self-rated driving skills remained unchanged. The findings indicate that frequent medicinal cannabis users may not accurately judge their own hazard perception performance, yet they adopt cautious driving behaviors after THC use.
Psychopharmacology
December 13, 2025
David Greguš, Jaroslav Hlinka, Filip Tylš et al.
The spatial organization of the cingulate cortex, rather than the thickness of a single region, predicts the intensity of psychedelic experiences under psilocybin. In a double-blind, placebo-controlled crossover study with 25 healthy participants, an anterior–posterior gradient in cingulate thickness significantly predicted psychedelic experience intensity. The previously reported finding that rostral anterior cingulate cortex thickness alone predicts emotional responses showed a comparable effect size but did not reach statistical significance, likely due to the smaller sample size. These results suggest that the pattern of cortical thickness across the cingulate cortex, not focal measures, serves as a neuroanatomical marker of variability in psychedelic response.
Psychopharmacology
November 15, 2025
Elisabetta Ciccocioppo, Sara Massetti, Marcus W Meinhardt et al.
Alcohol use disorder (AUD) is a major medical problem with limited treatments. (R)-ketamine, a form of the dissociative psychedelic with fewer dissociative and anesthetic effects than the racemic mixture, reduced alcohol consumption in female but not in male Marchigian Sardinian alcohol-preferring (msP) rats when given orally at doses of 10, 20, and 40 mg/kg in a two-bottle free choice 24-hour drinking paradigm. No effect was observed on alcohol self-administration. (R)-ketamine also attenuated the retrieval of alcohol-related memories in female but not in male rats. These results suggest (R)-ketamine attenuates alcohol-related behaviors in a sex-dependent manner, with females showing higher sensitivity, supporting clinical investigation in patients with AUD.
Psychopharmacology
November 10, 2025
Yair Dor‐ziderman, Jonathan David, Aviva Berkovich‐ohana
Preliminary evidence suggests that ayahuasca can change how people think about and feel toward death at conscious levels, but automatic, unconscious perceptual processes that deny death remain unaffected.
Psychopharmacology
October 31, 2025
Vítor Bruno, Lídia Emmanuela Wiazowski Spelta, Matheus Lujan Pereira et al.
Ayahuasca, a brew containing DMT and β-carbolines used in indigenous rituals, has shown potential for treating substance use disorders. In C57Bl/6 mice, ayahuasca at a high dose (15 mg DMT/kg) induced rewarding effects, but these were weaker than those of cocaine. When mice were conditioned with cocaine and later treated with ayahuasca (12.5 or 15 mg DMT/kg), the brew prevented the reinstatement of cocaine-induced conditioned place preference after a cocaine challenge. The findings suggest ayahuasca may have therapeutic value for cocaine use disorder by reducing relapse to drug-seeking behavior.
Psychopharmacology
October 27, 2025
David A Bender, Sandeep M Nayak, Joshua S Siegel et al.
Providers administering psychedelic drugs in clinical trials report a range of challenges, including intense dysphoria during sessions (42% of respondents), disappointment with the intervention (25%), and re-engaging with traumatic experiences (17%). An anonymous survey of 40 qualified respondents who oversaw 1656 psychedelic sessions identified 11 distinct themes of challenges. 70% of respondents felt that individuals with PTSD or prior trauma need additional psychological support, and they recommended an average of 9.8 hours of total psychological support for first-time recipients with serious mental illness. These findings highlight the need to incorporate potential adverse experiences into psychological support protocols for clinical trials and future guidelines.
Psychopharmacology
October 27, 2025
Nina Gregoire, Ethan Klukas, Kimberley Kaseweter et al.
Three personality profiles—Easygoing Extraverts, Average, and Reserved Introverts—emerged among 184 patients receiving ketamine-assisted therapy at a Canadian clinic. Reserved Introverts had more severe baseline depression and anxiety. All profiles showed improvements in depression and anxiety one week after treatment, but personality did not predict differential symptom change. Patients with a trauma history experienced greater reductions in depression and improvements in physical quality of life than those without. Personality relates to baseline mental health severity but not short-term treatment response, while trauma history may indicate greater benefit from ketamine therapy.
Psychopharmacology
October 11, 2025
Michelle St Pierre, Elena Argento, Jordyn Cates et al.
On days when adults microdose psychedelics, they report higher levels of wellbeing, productivity, creativity, connectedness, contemplation, and focus compared to days they do not microdose. The increase in creativity is especially pronounced among people who have previously used larger doses of psychedelics. These findings come from a large international survey of 1,435 adults who microdose, using daily-level self-reports that reduce reliance on memory. Because the study is observational and exploratory, the results should be interpreted cautiously.
Psychopharmacology
April 22, 2025
Anthony N Nist, Stephen J Walsh, Timothy A Shahan
Adding electric footshock punishment to the probabilistic reversal learning task increased behavioral persistence and cognitive flexibility in rats, but a single dose of ketamine had no effect beyond causing acute impairments. The experiment used 40 rats and compared those receiving footshock for non-rewarded trials with those receiving only timeout periods. The findings suggest that punishment conditions significantly affect task performance and support previous evidence that ketamine may not influence cognitive flexibility or reward processing in healthy rats.
Psychopharmacology
July 1, 2024
Dilan Gokalp, Gunes Unal
Ketamine's antidepressant effect requires suppressed activity of the metabotropic glutamate receptor 5 (mGluR5). In adult male Wistar rats, enhancing mGluR5 activity with the drug CDPPB blocked ketamine's antidepressant effect in the forced swim test without affecting locomotion. Combining a low dose of ketamine (1 mg/kg) with the mGluR5 antagonist MTEP produced a robust synergistic antidepressant effect. However, this combination eliminated the anxiolytic effect seen with either drug alone. The findings indicate that mGluR5 antagonism can boost ketamine's antidepressant effectiveness at low doses, but at the cost of its anxiety-reducing properties.
Psychopharmacology
October 1, 2022
Daiane Momo Daneluz, Jeferson Machado Batista Sohn, Gabriela O Silveira et al.
Ayahuasca, a psychedelic brew containing DMT and β-carbolines, impairs fear memory reconsolidation in rats when given 20 minutes before or 3 hours after memory retrieval. A dose of 60 mg/kg was effective at both time points and did not produce an anxiolytic effect. The impairment lasted at least 22 days with no spontaneous recovery or reinstatement of fear. The effect depended on memory retrieval; without retrieval, ayahuasca did not impair reconsolidation. These findings suggest ayahuasca disrupts both early and late stages of memory reconsolidation rather than facilitating fear extinction.
Psychopharmacology
January 1, 1977
Herbert Y. Meltzer, Richard G. Fessler, Miljana Simonovic et al.
Lysergic acid diethylamide (LSD) at doses of 0.05 mg/kg and 0.20 mg/kg significantly lowered plasma prolactin levels in male rats. The higher dose also blocked prolactin increases caused by chlorpromazine and alpha-methylparatyrosine, drugs that reduce dopaminergic inhibition of prolactin secretion. LSD was more potent than methysergide, a serotonin blocker, in lowering prolactin, and more potent than apomorphine, a dopamine agonist, in blocking prolactin rises from quipazine, a serotonin agonist. These results suggest LSD acts as a potent dopamine agonist on pituitary or hypothalamic receptors that inhibit prolactin secretion.