Psychopharmacology
March 26, 2025
Laura Ley, Matthias E Liechti, Anna M Becker et al.
3 citations
Healthy volunteers enroll in psychedelic trials primarily out of interest in the substances and the appeal of the study setting, hoping for personal development and transformative experiences. In a series of six double-blind, placebo-controlled trials involving 151 participants, positive experiences were promoted by music, access to nature, and a trusting relationship with the investigator. A sterile hospital environment, lack of investigator support, and investigator-induced discomfort were criticized. Most volunteers felt their expectations were exceeded and would take the substances again, ideally in a natural setting with friends. Four key factors for positive study experiences are a secure interpersonal relationship, an aesthetically pleasing environment, access to nature, and music.
Psychopharmacology
January 18, 2025
Sharon R Sznitman, Yoel A Behar, Sheila Daniela Dicker-Oren et al.
3 citations
In a non-clinical sample of 36 adults attending a 4-day ayahuasca retreat, positive affect and mindfulness skills improved while negative affect decreased in the days following the retreat compared to before. Acute experiences such as feelings of transcendence, emotional breakthrough, and challenging experiences predicted greater positive affect afterward, but none of these acute experiences were linked to improvements in negative affect or mindfulness. No participants showed clinically significant adverse responses, and only 5.5% showed some degree of potentially clinically significant deterioration in affect. The findings suggest ayahuasca may improve mood and mindfulness, with certain acute experiences contributing specifically to increased positive affect.
Psychopharmacology
June 1, 1977
Sergio Solbes Ferri, Roser Reina, C. Spadaro et al.
3 citations
In rabbits, the narcotic antagonist naloxone does not block pain relief (antinociception) caused by 100 micrograms per kilogram of mescaline injected into the brain, but pretreatment with 6-hydroxydopamine (6-OHDA) does prevent this effect. 6-OHDA also prevents the stereotyped behavior that follows central mescaline administration. Because 6-OHDA destroys nerve terminals that contain catecholamines, the findings suggest that catecholamines play a crucial role in the effects produced by the hallucinogen mescaline when given centrally to rabbits.
Psychopharmacology
January 1, 1975
R. Utzinger
3 citations
Rabbits produced antibodies that specifically bind mescaline after being immunized with conjugates of bovine serum albumin and mescaline or its analogue 3,4,5-trimethoxyphenylacetic acid. Immunized rats that received mescaline showed behavioral differences compared to non-immunized controls, suggesting that the antibodies altered the drug's effects.
Psychopharmacology
March 1, 2026
Patricia Di Ciano, Sampson Zhao, Pamela Kaduri et al.
2 citations
Taking a low-dose cannabis edible (average 7.3 mg of THC) leads to measurable decreases in verbal learning and memory, specifically on two measures of a free recall task, 150 minutes after ingestion. No effects were found on visual attention or executive function as measured by the useful field of view and trail making tests. Subjective feelings of intoxication increased, but blood THC levels did not correlate with any cognitive performance changes. The results suggest that people who use relatively low doses of cannabis edibles may experience some cognitive decrements while feeling intoxicated.
Psychopharmacology
June 1, 2025
Carmen Abate, Richard Young, Malgorzata Dukat et al.
2 citations
The drug α-ethyltryptamine (α-ET), once used as an antidepressant and structurally related to the hallucinogen α-methyltryptamine, produces stimulus effects in rats that are similar to those of the phenylalkylamines MDMA (Ecstasy) and MDA (Love Drug). Rats trained to discriminate α-ET from saline showed full generalization to both MDMA and MDA. Four synthetic analogs of α-ET produced varied results: 4-OMe α-ET showed negligible α-ET-like effects, 5-OMe α-ET modest effects, while 6-OMe α-ET and 7-OMe α-ET fully generalized but with a narrow dose range for the former. α-ET appears to exert a complex stimulus combining features of MDMA, MDA, hallucinogens, and stimulants, suggesting it is a tryptamine counterpart to these phenylalkylamines.
Psychopharmacology
June 1, 2025
Bahar Yuksel, Zeynep Sen, Gunes Unal
2 citations
A single antidepressant dose of ketamine (10 mg/kg) given to adult Wistar rats partially impaired fear extinction when administered before fear acquisition or retrieval, but did not affect encoding or retrieval of cued fear or spatial memory. In the Morris Water Maze, ketamine facilitated memory modulation and reduced escape latency during the first day of reversal training when given before training or reversal sessions. The drug did not impair acquisition or retrieval processes in either implicit (fear) or explicit (spatial) memory tasks, but exerted opposing effects on memory modulation: disrupting fear extinction while facilitating reversal spatial learning.
Psychopharmacology
April 23, 2025
Jonathan David, Aviva Berkovich-Ohana, Yair Dor-Ziderman
2 citations
People who regularly use ayahuasca show lower death anxiety, less fear of death, less avoidant behavior around death, and greater acceptance of death compared to non-users. A cross-sectional study of 54 ayahuasca veterans and 53 non-users measured these differences using questionnaires and behavioral tasks. The differences were not explained by demographics, personality, mindfulness, beliefs about the afterlife, or awareness of impermanence. Instead, acceptance of impermanence—the willingness to embrace life's transience—was the key mechanism. Among ayahuasca users, the intensity of lifetime ego-dissolution experiences predicted how much they accepted impermanence. This suggests that acute psychedelic experiences can foster lasting changes in how people process mortality, and that promoting impermanence acceptance may help manage existential fear.
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.