Psychopharmacology
January 1, 1975
Ian E. Lush
2 citations
Male mice from seven inbred strains (A2G, C57BR, C3H, F/st, CBA, ICFW, and Schneider) were tested for hexobarbitone sleeping time. The same strains had previously been tested for the inhibitory effect of mescaline on emotional defecation. A strong correlation between the two measures across strains was found, which was unexpected theoretically and may have important implications for pharmacogenetics.
Psychopharmacology
February 7, 2026
Rebecca J Simpson, Mario F Juruena
1 citation
Ketamine-assisted psychotherapy (KAP) shows promise for treatment-resistant depression, with reductions in depressive symptoms sustained up to six months in some cases. However, among the three studies with control groups, no significant differences were found between KAP and control conditions. Methodological heterogeneity across the 11 included studies—including variability in treatment protocols, outcome measures, and study designs—limits the ability to draw firm conclusions or identify mechanisms driving KAP's effects. More rigorous research, particularly randomized controlled trials, is needed to better understand its efficacy and mechanisms.
Psychopharmacology
February 2, 2026
Benjamin Anderson, Andrew Winokur, Grace Chan
1 citation
Intranasal esketamine, approved by the FDA in 2019 for treatment-resistant depression (TRD), showed real-world effectiveness in a clinical setting in Hartford, Connecticut. In a sample of 50 patients whose moderate to severe baseline depressive symptoms were measured with the Montgomery-Asberg Depression Rating Scale (MADRS), symptoms reduced to the mild range after 4 weeks, and this improvement was sustained over 16 weeks of treatment. Adverse effects were transient and generally mild, with dissociation and sedation being most common; there were no safety events, misuse, or dependence, and very few discontinuations due to tolerability. The findings indicate that intranasal esketamine augmentation therapy is safe and effective in routine clinical practice.
Psychopharmacology
February 1, 2026
Ana Deutsch, Connor J Haggarty, Gavin N Petrie et al.
1 citation
A single oral dose of methamphetamine (20 mg) reduced blood levels of the endocannabinoid 2-AG in healthy adults, while MDMA (100 mg) did not. Neither drug affected anandamide (AEA) levels. Under placebo, higher AEA concentrations were linked to disliking the drug effects, suggesting a connection between AEA and negative expectations. These findings show how stimulants act on the endocannabinoid system and may inform treatments for substance use disorders.
Psychopharmacology
November 15, 2025
Michael H Baumann, Grant C Glatfelter, Sara E Walton et al.
1 citation
Intranasal delivery of the psychedelic compound N,N-dimethyltryptamine (DMT) is feasible and produces rapid drug uptake in rats. DMT given intranasally or subcutaneously caused similar effects, including increased flat body posture and decreased body temperature. Intranasal administration led to faster pharmacokinetics, with a half-life range of 11.9–14.3 minutes compared to 45.5–122.7 minutes for subcutaneous delivery, and higher peak drug concentrations. Importantly, maximal DMT concentrations in rats receiving low intranasal doses (30.2–55.6 ng/mL) overlap with psychoactive levels reported in humans, suggesting this non-invasive route may be viable for therapeutic use.
Psychopharmacology
November 5, 2025
Milad Soltanzadeh, Wang Zheng, Shona G. Allohverdi et al.
1 citation
Ketamine and psilocybin, two drugs with therapeutic potential for depression, produce distinct effects on brain electrical activity. Ketamine disrupts the balance between excitation and inhibition in neural circuits, as shown by changes in the aperiodic components of EEG spectra, and reduces beta band activity. Psilocybin also reduces alpha power in similar brain regions but does not affect beta activity or aperiodic components in the same way. These differences reflect their different mechanisms: ketamine blocks NMDA receptors while psilocybin targets serotonin receptors. Ketamine's unique EEG signature supports its role as a model for prodromal psychosis.
Psychopharmacology
August 11, 2025
Jussi Jylkkä, Aila Mustamo
1 citation
Most psychedelic researchers (85%) have personal experience with classic psychedelics. They view such experience as beneficial for research but also recognize it as a potential source of bias. Researchers acknowledge the importance of self-reflection and disclosing personal experiences, yet find disclosure challenging in practice. Personal use predicts more positive opinions about psychedelics' potential to improve well-being, transform society, address the ecological crisis, and answer spiritual questions. The findings highlight the prevalence of personal experiences among this sample and their influence on research interests and opinions, underscoring the need for open discussion and reflection.
Psychopharmacology
May 8, 2025
Agnieszka Pałucha-Poniewiera, Anna Rafało-Ulińska, Agata Faron-Górecka et al.
1 citation
In a mouse model of depression, (R)-ketamine altered mGlu5 receptor availability in several brain regions, reversing stress-induced changes in the hippocampus. Adding a partial mGlu5 receptor negative allosteric modulator (M-5MPEP) boosted the effectiveness of a subeffective dose of (R)-ketamine, reducing apathy- and anhedonia-like behaviors. These behavioral improvements were accompanied by changes in hippocampal eEF2 and TrkB protein levels. The findings suggest that weakening mGlu5 receptor function in the hippocampus may contribute to (R)-ketamine's antidepressant-like effects, and combining it with M-5MPEP could enhance its antidepressant activity.
Psychopharmacology
April 21, 2025
Noah N T Barr, Kayla J Giese, Sam G Moreton
1 citation
A systematic review of 31 studies found largely consistent evidence that psychedelic experiences can change attitudes towards death and reduce death anxiety in both clinical and non-clinical populations. However, significant gaps remain in understanding the role of set and setting, differences across psychedelic substances, underlying psychological mechanisms, the potential for worsening death anxiety, and the influence of expectancy and placebo effects. Less is known about the reliability and strength of these effects, the conditions under which they emerge, and which aspects of the experience best predict them.
Psychopharmacology
July 14, 2026
Kyla M Whitelock, Kaitlin R Van Alstyne, Liam J Conaboy et al.
6-APB, a recreational drug similar to MDMA, produces effects at very low doses (0.01 and 0.1 mg/kg) in mice, while impairing short-term fear memory and long-term context memory at 5 mg/kg. It also causes modest locomotor sensitization and may produce addiction. Reduced shock reactivity appears due to ataxia rather than analgesia. The behavioral profile broadly resembles MDMA, but amnesic effects emerge at higher doses than MDMA, and there is a larger gap between potential therapeutic doses and doses causing cognitive deficits. These findings suggest 6-APB may not be a low-risk therapeutic alternative to MDMA.
Psychopharmacology
July 14, 2026
Helena D Aicher, Joëlle Dornbierer, Luzia Caflisch et al.
A combination of harmine and DMT, the active ingredients in ayahuasca, reduces feelings of embarrassment and shame in healthy men. In a randomized trial with 28 participants, those who received the combination reported significantly less embarrassment when listening to recordings of their own singing compared to those who received a placebo. The treatment also lowered overall shame scores. Harmine alone did not produce these effects. The findings suggest that this compound may help treat psychiatric disorders where negative self-focused emotions play a key role.
Psychopharmacology
July 1, 2026
Sarah Ann Smith, Haseeb Mohammad, Lik Hang N Lee et al.
A review of 20 studies examined whether psychedelic drugs can affect social cognition in people with psychiatric or neurodevelopmental disorders that involve cognitive impairment. The drugs studied were ketamine, MDMA, psilocybin, LSD, and ayahuasca, tested in depressive disorders, anxiety disorders, autism spectrum disorder, and post-traumatic stress disorder. Findings included neural activation patterns suggesting that ketamine and psilocybin may modulate processes relevant to social perception, especially facial emotion processing, in depressive disorders. MDMA was linked to improvements in self-reported psychosocial functioning, self-awareness, and self-compassion in participants with PTSD. Direct evidence of improved social-cognitive functioning remains limited.
Psychopharmacology
June 20, 2026
E. C. H. M. Haijen-Bongers, P.p.m. Hurks, J. Schepers et al.
In adults with attention-deficit hyperactivity disorder, six weeks of biweekly low-dose lysergic acid diethylamide (20 µg) produced a limited effect on temporal processing, specifically on a time reproduction task, but did not improve performance on other neuropsychological measures of attention, inhibition, or motivational processing. The finding was observed in a secondary analysis of a double-blind, placebo-controlled trial with 46 completers. Baseline performance predicted some treatment outcomes differently between the LSD and placebo groups. The authors caution that the single positive result should be interpreted cautiously, especially because the parent trial showed no corresponding improvements in clinical symptoms.
Psychopharmacology
June 17, 2026
Pierre Klintefors, Chiranth Bhagavan, Richard Kanaan et al.
Low to moderate doses of psilocybin (5–20 mg) do not meaningfully disrupt manual dexterity or hand coordination in healthy adults. In a blinded trial, participants showed a modest biphasic dose-response pattern at higher doses (10–20 mg): slight impairment during peak effects and slight improvement 4.5 hours after administration, but effect sizes were small compared to baseline variability. Kinematic analyses found no substantial changes in movement smoothness or velocity, and the latent coordination structure remained stable, though finger movements showed a subtle increase in complexity. These results support the feasibility of combining psilocybin with active motor rehabilitation.
Psychopharmacology
June 10, 2026
Julian Kirsch, C. Poppe, Anne Beck et al.
Most people with alcohol use disorder (AUD) are aware of psychedelic research and would be willing to try psychedelic therapy, but their openness depends heavily on expecting it to succeed. In a mixed-method study of 112 participants from two non-psychedelic clinical trials and 10 patients from addiction outpatient services, 62.5% knew about psychedelic research and 64.3% were willing to join a psychedelic therapy trial. Willingness was strongly linked to higher expectations of research success, not to age or knowledge alone. Interviews revealed a spectrum of attitudes shaped by perceived therapeutic potential, fears of addiction or loss of control, personal and societal experiences with substances, and media exposure. Expectation of benefit was central to openness.
Psychopharmacology
May 28, 2026
Mazen A Atiq, Eli Weisman, Rodrigo B Guerra et al.
A healthy 35-year-old man experienced a rare hypotensive adverse event—neurocardiogenic syncope (fainting)—about 60 minutes after taking 25 mg of oral psilocybin in a clinical trial. His blood pressure dropped to 93/51 mmHg, with rapid heart rate and sweating, but he stabilized quickly with leg elevation and oral hydration. The episode may have been triggered by upright seated posture, restrictive EEG equipment, and anxiety about upcoming transcranial magnetic stimulation. Fewer than one-quarter of contemporary psychedelic trials report systematic adverse event assessment, highlighting the need for transparent documentation of both hypertensive and hypotensive events as psilocybin moves toward potential FDA approval.
Psychopharmacology
April 29, 2026
Anne-Fiona Griesfeller, Lotte Kooman, Lilian Kloft-Heller et al.
A scoping review of 53 sources found no coherent explanation for how psychedelics might recover repressed memories, nor consistent evidence that they do so reliably. Most publications focused on LSD, but few defined what they meant by repressed memory. Proposed mechanisms—psychoanalytical reductions of defensive memory blockades and neurobiological alterations of executive control—lacked empirical support. The review concludes that future work should provide clear definitions, test effects across multiple psychedelic substances, use placebo-controlled designs, and account for the potential occurrence of false memories.
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.