Progress in Neuro-Psychopharmacology and Biological Psychiatry
June 10, 2012
Daniel I. Brierley, Colin Davidson
133 citations
Ayahuasca, a hallucinogenic botanical mixture from the Amazon, is now used globally. Its main constituents are DMT, a hallucinogen, and harmine, a monoamine oxidase inhibitor that prevents DMT's rapid breakdown. Recent developments include online sales and substitution with related botanical or synthetic compounds. Ayahuasca use appears to improve mental health and reduce recidivism to alcohol and cocaine misuse. This review discusses ayahuasca's pharmacology, focusing on harmine, and suggests mechanisms for reduced recidivism, including MAOI effects, actions at 5-HT(2A) and imidazoline receptors, and inhibition of DYRK1A and the dopamine transporter. The therapeutic potential of harmine in other CNS conditions is also speculated upon.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
January 10, 2012
Evan J. Kyzar, Christopher Collins, Siddharth Gaikwad et al.
122 citations
Mescaline and phencyclidine (PCP) dose-dependently increased top activity in the novel tank test, reduced immobility, and disrupted swimming patterns in zebrafish. PCP, but not mescaline, evoked circling behavior in the open field test. At the highest doses tested, mescaline markedly increased shoaling behavior, while PCP did not affect it. Whole-body cortisol levels were unchanged by 20 mg/l mescaline but elevated by 3 mg/l PCP. These findings indicate that zebrafish models are sensitive to hallucinogenic compounds, producing complex behavioral and physiological effects.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
July 30, 2006
Eiji Shimizu, Hiroyuki Watanabe, Takashi Kojima et al.
103 citations
A 27-year-old man experienced substance intoxication after a single ingestion of what he believed was pure methylone powder purchased online. Chemical analysis revealed the powder contained about 60% methylone (120 mg) and 38% 5-MeO-MIPT (76 mg), a mixture not disclosed to the user. The case highlights that clinicians should be alert to intoxication from these agents and that substance-related mental disorders may be complicated by the combined use of multiple psychoactive drugs, especially when the actual composition of purchased drugs is unknown.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
June 28, 2022
Antonio Inserra, Antonella Campanale, David Cheishvili et al.
39 citations
Repeated administration of lysergic acid diethylamide (LSD) to mice over seven days altered DNA methylation at 635 sites and changed the expression of 178 proteins in the prefrontal cortex. The affected genes and proteins are involved in nervous system development, axon guidance, synaptic plasticity, and cell viability. Four specific genes—Coro7, Pef1, Rps24, and Abhd6—showed both increased methylation and increased transcription. These results suggest that LSD modifies epigenetic and protein-expression pathways related to neuroplasticity, which may underlie its therapeutic effects in mental disorders.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
May 1, 1998
Scott Helsley, David Fiorella, Richard A. Rabin et al.
30 citations
In rats trained to distinguish LSD from saline, several N-substituted tryptamines produced intermediate levels of LSD-like responding: MDMT (76.4%), DMT (77.9%), and DET (48.7%). 6-F-DET elicited 41.3% LSD-appropriate responding at 6.0 mg/kg, but only 4 of 8 subjects completed the session, precluding statistical analysis. Bufotenine (25.8%) failed to substitute. None of the tryptamines substituted completely for LSD, though the pattern aligns with their known human hallucinogenic activity. Among beta-carbolines tested, only harmane showed intermediate substitution (49.5%); others, including harmaline and THBC, showed no significant generalization. The tryptamines overall showed greater similarity to the LSD stimulus than the beta-carbolines did.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
January 31, 2025
Júnia L. de Deus, Juliana Marino Maia, Renato Nery Soriano et al.
27 citations
Psychedelics like psilocybin, LSD, and DMT show promise for reducing neuroinflammation linked to Alzheimer's, Parkinson's, and major depressive disorder. They act mainly through serotonin 5-HT2A receptors, lowering pro-inflammatory cytokines, regulating microglial activity, and shifting metabolite balance toward neuroprotection. They also influence NF-κB, PI3K/Akt, and mTOR pathways, promoting neuroplasticity and anti-inflammatory effects. Other neurotransmitter systems—glutamatergic, dopaminergic, noradrenergic, GABAergic, and cholinergic—contribute to these effects. The review highlights psychedelics as potential treatments for neuroinflammatory and neuropsychiatric disorders.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
September 7, 2024
Zhen Xuen Brandon Low, Wei Shen Ng, Bey Hing Goh et al.
19 citations
A systematic review of 40 preclinical studies found that classical psychedelics such as psilocybin, LSD, and DMT can reduce inflammation. In 29 of 36 studies measuring inflammatory cytokines, at least one cytokine decreased after psychedelic administration. Effects on immune cell activity were mixed, with half of 10 studies showing an increase and half a decrease. The compounds alleviated pre-existing inflammation but promoted inflammation when given under normal conditions. These findings may guide future clinical trials on psychedelics for inflammatory conditions.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
January 1, 2025
Zitong Wang, Brett Robbins, Ryan Zhuang et al.
15 citations
In a rodent model of chronic stress, psilocybin reduced behavioral despair and cognitive impairments. Twenty-two male Wistar rats were exposed to predator odor and social instability; those given psilocybin showed improvements in memory and mood-related behaviors compared to sham-treated stressed animals. The benefits appear to involve the endocannabinoid system dampening overactivity of the hypothalamic-pituitary-adrenal axis. The results suggest psilocybin may hold promise as an early intervention for stress-related mental health disorders.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
January 1, 2025
Ines Erkizia-Santamaría, Igor Horrillo, J. Javier Meana et al.
10 citations
Psilocybin, along with its active metabolite psilocin, shows promise as a treatment for neuropsychiatric disorders. Clinical trials report that psilocybin produces a large, rapid, and lasting improvement in symptoms of depression and anxiety, with a favorable safety profile of low toxicity and good tolerance. Preclinical studies in naïve animals and animal models of disease have yielded somewhat discrepant results in standard tests for depression- and anxiety-like behavior, but overall suggest positive outcomes. This review provides an overview of clinical trials of psilocybin-assisted psychotherapy and surveys up-to-date preclinical research, including rodent models used to study the neurobiological and behavioral actions of psilocybin and its primary molecular target, the serotonin 2A receptor.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
October 1, 2025
Marta L.c. Palhas, Rémi Corne, Raymond Mongeau
4 citations
Psychedelic treatments produce therapeutic effects within hours that persist beyond the drug's elimination, suggesting neuroplasticity-related mechanisms. Serotonergic psychedelics and ketamine recruit glutamatergic neurons to stimulate BDNF-trKB signaling, promoting synaptogenesis via the mTOR pathway, which may explain their efficacy in depression, anxiety, PTSD, and addiction. Ibogaine exerts effects through GDF-mediated mechanisms underlying its benefit in addiction. MDMA, used for PTSD, influences synaptogenesis via 5-HT2A-dependent effects on BDNF but appears to have deleterious effects on neurotrophic signaling in the hippocampus, impacting plasticity differently. The modulation of the neurotrophic system contributes to reducing depressive symptoms, but its role in PTSD and addiction remains less understood.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
January 1, 1986
A Fundarò, L Molinengo, M.c. Cassone et al.
4 citations
Rats given daily mescaline (4 or 10 mg/kg) showed no impairment in adapting their behavior when the schedule of food reinforcement changed from a fixed ratio to a fixed interval. However, in a reversal test where the rewarded lever was switched, chronic administration of 4 mg/kg/day made rats completely unable to switch to the newly reinforced lever. A higher dose of 9 mg/kg/day had an excitatory effect, causing rats to make more reinforced responses than unreinforced ones during the second and third reversals, exceeding the control group's performance.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
February 27, 2026
Chris H. Miller, Angela Hickman, Caitlin Baten et al.
2 citations
Ketamine, originally developed as an anesthetic, has emerged as a novel treatment for major depressive disorder (MDD) and treatment-resistant depression (TRD). Its antidepressant properties were discovered serendipitously, leading to FDA approval for TRD and MDD with suicidal ideation. The drug acts primarily as an NMDA receptor antagonist, triggering a paradoxical AMPA-mediated glutamate surge that promotes synaptogenesis and neuroplasticity. Intravenous ketamine and intranasal esketamine differ in dosing, bioavailability, and onset. Common adverse effects include dissociation, sedation, and hypertension. Efficacy studies show mixed-to-positive results, with non-inferiority to established treatments like electroconvulsive therapy. Future research aims to develop predictive markers for personalized medicine.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
October 1, 2025
Brandon Richardson, Antonio Inserra, Michael Pileggi et al.
2 citations
Psilocybin and lisuride both activate 5-HT2A receptors, but only psilocybin triggers the head twitch response (HTR) in mice, a proxy for hallucinogenic activity. In adult male C57BL/6N mice, psilocybin (0.3–3 mg/kg) inhibited serotonin neuron firing in the dorsal raphe nucleus via 5-HT2A receptors, while lisuride (0.1–0.5 mg/kg) did not. Both drugs reduced dopamine neuron firing in the substantia nigra, but lisuride's effect was more sensitive to 5-HT2A antagonism. Psilocybin elicited HTR; lisuride did not. Only high-dose lisuride reduced immobility in the forced swim test. Both drugs reduced locomotion in open field and elevated plus maze tests. Principal component analysis separated the drug effects, indicating distinct neurobiological pathways: psilocybin produces psychedelic-like, serotonin-dominant effects, while lisuride displays dopamine-linked improvements in coping behavior.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
September 24, 2025
Marie Celine Dorczok, Gloria Mittmann, Thomas Ettl et al.
2 citations
Psilocybin-assisted therapy combined with structured psychological support produces sustained reductions in depressive symptoms in people with treatment-resistant depression and major depressive disorder. Higher doses generally yield stronger benefits. Despite its potential as a holistic treatment, methodological limitations—including variation in study designs, inconsistent psychological support, and difficulty with blinding due to the drug's subjective effects—underscore the need for standardized protocols in future research to ensure reliable outcomes. Further work is needed to clarify the mechanisms behind its therapeutic effects.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
January 1, 1986
L Molinengo, M.c. Cassone, Alessandra Baroli et al.
2 citations
Chronic oral administration of mescaline at 30 mg/kg/day in rats accelerated the spontaneous decay of a conditioned reflex (memory decay) during a period without daily training in a staircase maze, with results statistically significant only at this dose. In a T maze with two lateral alleys closed by swinging doors, the same dose increased the time rats spent opening the first door. When doors were latched, mescaline also increased door-opening time. Mescaline increased food consumption, with the increase at 30 mg/kg/day being statistically significant.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
April 1, 2026
Yong-xing Qiao, Wei Dai, Yi-shan Yao et al.
1 citation
Psilocybin rapidly reversed depressive-like behaviors in mice subjected to chronic restraint stress, an effect comparable to ketamine. Both drugs prevented stress-induced loss of astrocytes and reduced levels of the A1 astrocyte marker C3 protein in the prefrontal cortex. The active metabolite psilocin stimulated primary astrocyte activation, proliferation, and release of ATP, lactate, and glutamate, and improved mitochondrial function. Psilocin also reversed impairments caused by A1 astrocytes. Depleting astrocytes in the prelimbic region of the medial prefrontal cortex diminished psilocybin's antidepressant action in unstressed mice, suggesting astrocytes play a key role in the drug's effects.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
February 18, 2026
Dimitri Henriques Daldegan-Bueno, C Donegan, Rachael L. Sumner et al.
1 citation
Taking very low doses of LSD (8 micrograms) repeatedly over a short period may temporarily improve mood in people with depression, though the effect needs confirmation in controlled experiments. The drug's behavior in the body was measured in this group, and no evidence of tolerance or increased sensitivity appeared, even when the dose was gradually increased.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
February 10, 2026
Chiranth Bhagavan, Olivia P. Carter, Alexander Bryson et al.
1 citation
Functional disorders, where symptoms lack an organic explanation, are difficult to treat with existing therapies. This review of 55 studies found that classic psychedelics, particularly LSD in older studies and psilocybin in newer trials, show potential for treating these conditions. 60.7% of studies reported improvement, primarily for functional neurological symptoms. However, the evidence is limited by mostly observational designs, few control groups, and a lack of long-term data. Adverse events included acute psychological and physical effects, and transient worsening of functional symptoms. Future research needs standardized protocols and better safety assessments.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
January 1, 2026
Cheng-Teng Ip, Sebastian Olbrich, Mateo de Bardeci et al.
1 citation
In a double-blind, randomized, crossover, placebo-controlled trial with 25 healthy adults, psilocybin (10–20 mg oral) decreased EEG power in slow frequency bands (theta and alpha) and increased power in fast frequency bands (beta, gamma1, gamma2) compared to placebo. Connectivity within the default-mode network and localized parietal network increased under psilocybin. Changes in EEG power and connectivity correlated positively with subjective experiences measured by the Altered States of Consciousness Questionnaire. Baseline EEG features predicted subjective alterations, suggesting that specific brain activity patterns could serve as biomarkers for tailoring psilocybin therapy.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
August 1, 2025
Sofía Villalba, Sofia Bosch, Lucia di Constanzo et al.
1 citation
Noribogaine, the primary metabolite of the atypical psychedelic ibogaine, alters thalamic calcium channel gene expression and current density in mice in a sex- and 5-HT2A receptor-dependent manner. A single injection of 10 mg/kg noribogaine increased CACNA1g (T-type) mRNA expression only in wild-type males and knockout females, indicating receptor- and sex-specific effects. The same dose increased CACNA1a (P/Q-type) expression in both sexes and decreased HCN2 expression in females of both genotypes but only in knockout males. Bath-applied noribogaine (50 μM) blocked T-type calcium current density only in knockout females, not in wild-type females or males. Baseline calcium current density was also higher in female ventrobasal neurons, further suggesting sex-dependent differences.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
July 1, 2026
Guilherme Lodetti, Rafael Mariano de Bitencourt, Antonio Inserra et al.
A single dose of Ayahuasca reduced relapse-like alcohol drinking in alcohol-dependent rats, with effects varying by sex and alcohol concentration. It also lessened anxiety- and depression-like behaviors caused by alcohol withdrawal, increased dopamine in the striatum of both male and female rats, and restored serotonin levels in the cortex primarily in males. Ayahuasca partially reversed alcohol-related drops in brain-derived neurotrophic factor and reduced markers of oxidative stress in the frontal cortex, hippocampus, and striatum. However, antioxidant enzyme activities were not consistently altered, and some neurochemical and oxidative stress measures showed only partial normalization. The findings suggest Ayahuasca modulates multiple neurobiological pathways disrupted by chronic alcohol exposure, with region- and sex-dependent effects.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
February 8, 2026
Michael J. Haupt, Savannah Pointe, Kevin F. Boehnke et al.
Ayahuasca, a psychedelic plant brew with centuries of traditional use in Central and South America, has drawn increased drug tourism and scientific interest for potential health benefits. A systematic review of 18 prospective studies found long-term changes in wellbeing, depression, psychiatric symptoms, substance misuse, cognitive flexibility, personality, and prosocial behavior among mostly unselected volunteers at retreat centers. While population-level mental health improvements were noted, some participants experienced persisting psychiatric complications. No prospective studies examined physical health conditions, though one reported decreased physical pain and another lasting neurometabolic changes in the posterior cingulate cortex. Limitations include small samples, unstandardized dosages, and lack of control groups.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
November 22, 2025
Shakila Meshkat, Noah Chisamore, Zoe Doyle et al.
A single dose of psilocybin was linked to small, temporary gains in processing speed and executive function in people with treatment-resistant depression. These cognitive improvements seemed unrelated to mood changes but did not consistently surpass the improvements expected from simply retaking the tests. The findings underscore the need for larger, controlled studies to determine whether psilocybin genuinely enhances cognition or if the observed changes stem from practice effects or mood shifts.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
October 23, 2025
Danielle Bukovsky, Aron Amaev, Jianmeng Song et al.
A systematic review of 42 clinical studies involving 1,068 participants found that psilocybin, when administered in controlled settings, has a favorable safety profile. Common adverse events included headache, transient increases in blood pressure, and nausea, which typically resolved on their own. Serious adverse events were reported infrequently, in only 2 of the 42 studies, and were limited to participants with underlying depressive disorders, such as suicidal behavior or hospitalization. All studies had a high risk of bias due to concerns regarding blinding. The review provides an outline of common and uncommon adverse events, serious adverse events, and considerations for future protocols.