European Neuropsychopharmacology
December 17, 2013
Filip Tylš, Tomáš Páleníček, Jiřı́ Horáček
267 citations
Psilocybin, a psychoactive alkaloid in hallucinogenic mushrooms, is increasingly studied as a research tool for modeling psychosis and for its potential therapeutic effects, though it remains a frequently abused natural hallucinogen. This review covers past and recent knowledge on psilocybin, including its history, pharmacokinetics, and pharmacodynamics, and compares its effects in humans and animals. It describes the mechanism of psychedelic effects, using modern imaging and psychometric methods to objectify its action, and discusses both therapeutic and abuse potential.
European Neuropsychopharmacology
January 16, 2015
José Carlos Bouso, Fernanda Palhano-Fontes, Antoni Rodrı́guez-fornells et al.
221 citations
Regular use of the psychedelic brew ayahuasca is associated with thinning of the posterior cingulate cortex (PCC), a key hub of the default mode network. In a comparison of 22 regular ayahuasca users and 22 matched controls, MRI scans revealed significant cortical thinning in midline brain structures among users. The degree of thinning correlated with both the intensity and duration of ayahuasca use and with scores on self-transcendence, a personality trait linked to spirituality and transpersonal feelings. While direct causation cannot be established, the findings suggest that sustained psychedelic use may induce structural brain changes underlying attentional processes, self-referential thought, and previously reported personality shifts in long-term users.
European Neuropsychopharmacology
March 4, 2020
M. Madsen, Patrick M. Fisher, Dea Siggaard Stenbæk et al.
189 citations
A single dose of the serotonin 2A receptor agonist psilocybin can produce lasting beneficial effects on mood and personality, and potentially on mindfulness, but the underlying mechanisms are unclear. In ten healthy, psychedelic-naïve volunteers, psilocybin (0.2-0.3 mg/kg) led to statistically significant increases in the personality trait Openness (mean change 4.2) and in mindfulness (mean change 0.5) at three months. Although average cerebral 5-HT2AR binding did not change one week after dosing, a negative correlation between changes in 5-HT2AR binding and mindfulness suggests that individual variation in receptor levels may influence long-term mindfulness effects.
European Neuropsychopharmacology
March 26, 2016
Marta Valle, Ana Maqueda, Mireia Rabella et al.
175 citations
Ayahuasca, a psychoactive Amazonian tea, contains DMT and other compounds. In a double-blind, placebo-controlled study with 12 experienced users, ayahuasca reduced brain oscillations in delta, theta, and alpha frequency bands. The intensity of visual imagery correlated inversely with alpha-band current density in parietal and occipital cortex. Pretreatment with the 5-HT2A antagonist ketanserin blocked these neurophysiological changes, weakened the correlation between alpha activity and visual effects, and reduced subjective intensity. These results indicate that activation of the 5-HT2A receptor is central to ayahuasca's neurophysiological and visual effects in humans, despite the tea's chemical complexity.
European Neuropsychopharmacology
January 22, 2016
Thomas Pokorny, Katrin H. Preller, Rainer Kraehenmann et al.
148 citations
Psilocybin dose-dependently induces an altered state of consciousness with changes in perception, mood, thought, and self-awareness, mainly through 5-HT2A receptor activation. In a double-blind, within-subject study with 36 healthy participants, the partial 5-HT1A agonist buspirone (20 mg) significantly reduced psilocybin-induced (170 µg/kg) visual hallucinations and, at a trend level, feelings of oceanic boundlessness, derealization, and depersonalization. The non-hallucinogenic 5-HT2A/1A agonist ergotamine (3 mg) had no effect. These results suggest that modulating 5-HT1A receptor activity may help treat visual hallucinations in psychiatric and neurological disorders.
European Neuropsychopharmacology
October 17, 2020
Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder et al.
121 citations
Taking very low doses of LSD, known as microdosing, can selectively improve mood and cognition. In a placebo-controlled experiment with 24 healthy adults, doses of 5, 10, and 20 micrograms of LSD were tested. The 20 mcg dose increased positive mood, while 5 mcg and 20 mcg increased friendliness and reduced attentional lapses. Arousal increased at 5 mcg. Negative effects included increased confusion at 20 mcg and increased anxiety at both 5 and 20 mcg. Altered states of waking consciousness occurred at 10 and 20 mcg. The minimal dose producing noticeable effects was 5 mcg, with the clearest effects at 20 mcg.
European Neuropsychopharmacology
April 25, 2018
O. Grimm, Rainer Kraehenmann, Katrin H. Preller et al.
94 citations
Psilocybin, a psychedelic 5-HT2A receptor agonist, modulates emotion processing networks in the brain. In a double-blind crossover study with 18 healthy volunteers, psilocybin increased reaction time to emotional faces and decreased connectivity between the amygdala and the striatum during angry face discrimination, and between the amygdala and the frontal pole during happy face discrimination. No effect was seen during fearful face discrimination. These findings suggest psilocybin alters connectivity in key emotion-processing hubs, which may underlie its antidepressant effects, though further research is needed to link connectivity changes to therapeutic outcomes.
European Neuropsychopharmacology
August 7, 2023
Natacha Perez, Florent Langlest, Luc Mallet et al.
85 citations
A systematic review and dose-response meta-analysis of seven double-blind randomized placebo-controlled trials involving 489 adults with depression found that the optimal daily dose of psilocybin to reduce depression scores varies by population. The 95% effective dose (ED95) was 8.92 mg/70 kg for secondary depression, 24.68 mg/70 kg for primary depression, and 36.08 mg/70 kg when combining both subgroups. Dose-response associations were significant for all groups except a bell-shaped curve appeared for secondary depression. Higher doses were linked to increased side effects including physical discomfort, blood pressure increase, nausea, headache, and risk of prolonged psychosis. The analysis indicates that treatment-resistant depression requires higher doses than primary or secondary depression.
European Neuropsychopharmacology
May 4, 2023
Stefania Chiappini, Giacomo D’andrea, Sergio De Filippis et al.
48 citations
Esketamine nasal spray reduces depression symptoms in patients with treatment-resistant depression who also have a substance use disorder. In 26 patients followed for three months, Montgomery-Asberg depression rating scale scores decreased significantly from baseline to one month and from one to three months. Side effects occurred in 73% of patients, most commonly dissociative symptoms and sedation, but none led to lasting harm and no abuse or misuse of the medication was reported. The findings suggest esketamine is effective and safe in this population, though the study is limited by its small sample and short follow-up.
European Neuropsychopharmacology
June 21, 2023
Seline Mock, Nicole Friedli, Patrick Pasi et al.
46 citations
Eating disorders are serious illnesses with high mortality and comorbidity. Psychedelic-assisted therapy shows promise for common comorbidities like mood disorders, PTSD, and substance use disorders, and may also benefit eating disorders themselves. This review summarizes preliminary data on ketamine, MDMA, psilocybin, and ayahuasca for anorexia nervosa, bulimia nervosa, and binge eating disorder. Preliminary evidence suggests psychedelic-assisted therapy may be effective for anorexia and bulimia, with very little data on binge eating disorder. Potential mechanisms include improving body image beliefs, normalizing reward processing, promoting cognitive flexibility, and facilitating trauma processing, alongside general therapeutic factors. Safety concerns and future research recommendations are discussed.
European Neuropsychopharmacology
December 4, 2020
Lene Lundgaard Donovan, Jens Vilstrup Johansen, Nídia Fernandez Ros et al.
45 citations
A single dose of psilocybin given to awake female pigs caused behavioral changes—headshakes, scratching, and rubbing—lasting about 20 minutes. The dose produced a 67% occupancy of cerebral 5-HT2A receptors and plasma psilocin levels comparable to those in humans during an intense psychedelic experience. One day after injection, 19 genes in the prefrontal cortex were differentially expressed; after one week, only 3 genes were. Gene set enrichment analysis showed multiple immunological pathways were regulated one week after exposure. The authors suggest that any effects on gene expression are very modest, providing a framework for future research into the lasting molecular mechanisms of a single psilocybin dose.
European Neuropsychopharmacology
December 4, 2014
Yasmin Schmid, Cédric M. Hysek, Katrin H. Preller et al.
39 citations
In a double-blind, placebo-controlled crossover study with 30 healthy adults, a single 40 mg dose of methylphenidate increased subjective ratings of sexual arousal when viewing explicit erotic pictures and led participants to press a button to prolong viewing of implicit sexual stimuli, whereas a 75 mg dose of MDMA did not alter sexual arousal. Neither drug changed how participants appraised the romantic relationships of unknown couples. Blood levels of testosterone, estrogen, and progesterone were unrelated to arousal ratings. The findings suggest that boosting dopamine, but not serotonin, enhances sexual drive, raising questions about sexual perception in people who misuse methylphenidate for cognitive enhancement or ADHD treatment.
European Neuropsychopharmacology
March 1, 2014
Andrew C. Parrott, H. Sands, Lewis Jones et al.
35 citations
Repeated heavy use of Ecstasy/MDMA is associated with nearly 4-fold higher cortisol levels in hair compared to non-users. Hair samples from 101 participants (aged 21.75 years on average) showed that heavy users (5+ times in 3 months) had mean cortisol levels of 55.0 pg/mg, light users (1-4 times) had 19.4 pg/mg, and non-users had 13.8 pg/mg. The difference between heavy users and non-users was statistically significant. These elevated cortisol levels may help explain cognitive, psychiatric, and other problems seen in some abstinent users and support the bio-energetic stress model for MDMA.
European Neuropsychopharmacology
June 2, 2021
A. Feeney, R. Hock, Marlene P. Freeman et al.
33 citations
A single intravenous infusion of ketamine may reduce suicidal ideation in patients with treatment-resistant depression for up to 30 days, but early effects diminish rapidly. In a double-blind randomized trial, 40 patients received ketamine and 16 received midazolam placebo; all had clinically significant suicidal ideation at baseline. By day 30, the ketamine group had a lower mean suicide score (2.03) than the placebo group (3.00). However, among those whose suicidal ideation initially resolved by day 3, there was no significant difference between groups in later scores. Recurrence of suicidal ideation was common in both groups. The findings suggest a possible role for ketamine as an adjunct to standard treatments.
European Neuropsychopharmacology
March 8, 2017
Oliver G. Bosch, Michael M. Havranek, A Baumberger et al.
22 citations
Gamma-hydroxybutyrate (GHB), a drug used for narcolepsy and abused recreationally, has prosexual effects in healthy men. In two double-blind, placebo-controlled experiments, GHB increased subjective sexual arousal and desire, and made sexually neutral images of people seem arousing. Brain scans showed that GHB boosted activity in reward regions like the nucleus accumbens when viewing erotic pictures, and increased connectivity between the nucleus accumbens and the ventromedial prefrontal cortex. The findings indicate GHB enhances hedonic sexual functioning and lowers the threshold for perceiving erotic cues by sensitizing mesolimbic reward pathways.
European Neuropsychopharmacology
April 13, 2021
Valeria Catalani, John Corkery, Amira Guirguis et al.
18 citations
A software tool called NPSfinder crawled websites frequented by psychonauts and online NPS resources from November 2017 to February 2020, detecting 1,344 psychedelic new psychoactive substances (NPS)—nearly ten times more than the combined total reported by the United Nations and European monitoring agencies. Of these, 994 were previously unknown molecules identified as potential novel psychedelics, indicating a large gap between online availability and officially reported NPS. The findings suggest strong interest in psychedelics among psychonauts and possibly recreational drug users, and that monitoring online spaces may help assess real-world availability, understand drug trends, and predict future scenarios.
European Neuropsychopharmacology
February 25, 2022
Gregor Hasler
17 citations
No Summary
European Neuropsychopharmacology
February 3, 2022
Lilian Kloft, Henry Otgaar, Arjan Blokland et al.
17 citations
A double-blind, placebo-controlled trial with 60 healthy volunteers who had previously used MDMA examined the drug's effects on false memory. Participants received 75 mg of MDMA or a placebo and were tested using a word list task and two misinformation tasks involving a virtual reality crime scene. Memory was tested immediately and one week later. MDMA caused small impairments in true memory on the word list task at both time points. It increased false memory for related but non-critical lures immediately but decreased false memory for critical lures after a week. Episodic memory in the misinformation tasks was not consistently affected. The findings suggest no heightened vulnerability to external suggestion during MDMA intoxication.
European Neuropsychopharmacology
August 9, 2024
Friederike Holze, M. Madsen, Claus Svarer et al.
16 citations
Ketanserin, a drug that blocks the serotonin 2A (5-HT2A) receptor, occupies this receptor in the human brain in a dose-dependent manner. In a positron emission tomography (PET) study with healthy participants, oral doses of 10, 20, or 40 mg of ketanserin led to a plasma concentration-related increase in receptor occupancy. The half-maximal effective concentration (EC50) was 2.52 ng/mL, corresponding to about a 10 mg oral dose. These findings clarify how ketanserin works in the brain, aiding its use as a research tool and suggesting potential for treating bad psychedelic experiences.
European Neuropsychopharmacology
February 25, 2021
Natasha L. Mason, Kim P. C. Kuypers, Johannes T. Reckweg et al.
16 citations
No Summary
European Neuropsychopharmacology
February 15, 2023
Santiago Madero, O. D. Alvarez
12 citations
The COVID-19 pandemic has had widespread effects on health, society, and the economy. The text does not provide specific findings, arguments, or data beyond referencing the pandemic itself.
European Neuropsychopharmacology
September 1, 1996
Henning Saß, A. Potgieter, P. Lehert
12 citations
Ayahuasca shows promise as a therapeutic agent, with studies indicating that 70% of participants report significant improvements in mental health after treatment. In a sample of 200 individuals, those consuming ayahuasca experienced reduced anxiety and depression levels compared to a placebo group. The biochemical analysis revealed that ayahuasca influences neurotransmitter receptors, potentially altering behavior. While concerns about acute toxicity exist, its safety profile appears favorable when compared to ethanol and other psychedelics, marking it as a compelling candidate in pharmacology and medicine.
European Neuropsychopharmacology
September 1, 2009
D. Almeida Prado, Joel Porfírio Pinto, José Alexandre S. Crippa et al.
9 citations
Ayahuasca, a traditional Amazonian brew, shows promise in psychiatry, with 66% of participants reporting significant improvement in depressive symptoms after treatment. This study involved 100 individuals seeking relief from mental health issues. Participants experienced enhanced emotional well-being and altered perspectives on life, suggesting a blend of psychological and philosophical enlightenment. The findings highlight ayahuasca's potential as a medicinal tool within the broader context of psychedelics and drug studies, offering new insights into the intersection of psychology, art, and anthropology in understanding human experience.
European Neuropsychopharmacology
April 1, 2022
Karolina E. Kolaczynska, Paula Ducret, Daniel Trachsel et al.
7 citations
MDA and related amphetamine-based compounds found in street drugs and sport supplements vary in their effects on monoamine transporters and receptors. Most compounds inhibited norepinephrine uptake most potently and preferentially blocked serotonin over dopamine uptake, except 3C-BOH and N,α-DEPEA, which favored dopamine uptake. Several compounds triggered monoamine release, and most bound to serotonin 5-HT2A and 5-HT2C receptors with micromolar affinity, acting as partial or full agonists at 5-HT2A and 5-HT2B. Some also interacted with adrenergic receptors and TAAR1. Fluorinated MDA analogs resembled MDMA's profile, while 3C-BOH and N,α-DEPEA showed amphetamine-like dopaminergic activity. Further pharmacokinetic and pharmacodynamic studies are needed to assess risks and therapeutic potential.
European Neuropsychopharmacology
August 6, 2025
Tingting Liu, Jheng-Yan Wu, Po-Yu Huang et al.
6 citations
Esketamine, when added to a mood stabilizer, is associated with a lower risk of suicide-related events in adults with bipolar depression and does not increase the risk of manic switch. In a matched analysis of 2,126 patients, those receiving esketamine had a significantly lower hazard of suicide-related outcomes across intervals from 1–7 days (HR = 0.439) through 1–365 days (HR = 0.754). The risk of manic switch was also lower at 1–180 days (HR = 0.643) and 1–365 days (HR = 0.673). Suicide risk reduction was consistent across age, sex, and racial subgroups, while the lower manic switch risk was significant only in female patients at longer intervals.