Frontiers in Pharmacology
April 18, 2024
Elad Lerer, Alexander Botvinnik, Orr Shahar et al.
14 citations
Psilocybin and a psilocybin-containing mushroom extract, but not the serotonin precursor 5-hydroxytryptophan, increased expression of immediate early genes cfos and egr1 in the somatosensory cortex of male mice. The head twitch response, a behavioral measure, did not correlate with gene expression changes. Blocking the 5-HT2C receptor enhanced psilocybin-induced egr2 expression, but other serotonergic modulators had no effect. These findings suggest that cfos and egr1 expression may be linked to psychedelic effects.
Frontiers in Pharmacology
December 3, 2020
Lauri Elsilä, Nuppu Korhonen, Petri Hyytiä et al.
13 citations
Acute doses of LSD at 0.025, 0.1, and 0.2 mg/kg did not alter reward-driven decision making in mice performing a touch-screen version of the Iowa Gambling Task, nor did the serotonin 2A receptor agonist 25CN-NBOH. The highest LSD dose (0.4 mg/kg) reduced premature responses and increased omission rates without affecting option selection. Amphetamine decreased correct responses and premature responding while increasing omission rates. Mice can perform previously learned decision-making tasks under LSD at commonly used doses.
Frontiers in Pharmacology
February 2, 2024
Joachim Neumann, Stefan Dhein, Uwe Kirchhefer et al.
12 citations
Hallucinogenic drugs like LSD, psilocybin, and DMT affect the brain by stimulating serotonin receptors, particularly 5-HT2A receptors, which likely causes their hallucinogenic effects. However, these drugs also act on the heart, potentially increasing the force of contraction and heart rate, and may lead to arrhythmias. This review examines the inotropic and chronotropic actions of bufotenin, psilocin, psilocybin, LSD, ergotamine, ergometrine, N,N-dimethyltryptamine, and 5-methoxy-N,N-dimethyltryptamine in the human heart.
Frontiers in Pharmacology
January 12, 2024
Ninon Freidel, Liliane Kreuder, Brenden Samuel Rabinovitch et al.
11 citations
Clinical trials of psychedelics for neurological and psychiatric disorders have systematically excluded people with past or current seizures, despite a lack of evidence that supervised psychedelic use causes or worsens seizures. No clinical trial or preclinical seizure model has shown that psychedelics induce seizures. This review presents cases where individuals experienced either seizures or seizure remission after psychedelic use, with the overall trend indicating safety in controlled clinical settings. The authors propose future research directions to include this population.
Frontiers in Pharmacology
August 22, 2023
Mary G. Hornick, Ashley Stefanski
9 citations
The opioid epidemic in the United States persists, with opioid use disorder (OUD) at its core, involving physical addiction, psychological issues, and social-legal problems. Existing treatments have limited effectiveness due to access barriers, strict regimens, and failure to address non-pharmacological aspects. A growing body of research suggests hallucinogens, particularly psychoplastogens like ibogaine, ketamine, and classic psychedelics, may offer a unique, holistic alternative by combining pharmacological, neuroplasticity, and psychological mechanisms. However, legal, social, and safety concerns have hindered research. This review examines preclinical and clinical evidence for these compounds in treating OUD, while noting that further research is needed to establish long-term efficacy and proper safety and ethical guidelines.
Frontiers in Pharmacology
May 24, 2024
Norman Nyazema, Jonathan Tinotenda Chanyandura, B. Egan
7 citations
Traditional medical practitioners in southern Africa use several indigenous psychoactive plants for divination and treating mental illnesses. A review of socio-pharmacological studies identified commonly used or abused plants including Boophone disticha, Cannabis sativa, Datura stramonium, Leonotis leonurus, Psilocybe cubensis, and Sceletium tortuosum. Commercialization of Cannabis, L. leonurus, S. tortuosum, and Aspalathus is growing rapidly, while abuse liability of B. disticha, D. stramonium, and P. cubensis appears underappreciated. Five countries have traditional medical practitioner policies, and three have councils. The authors suggest working closely with practitioners to reduce harm and explore therapeutic development of these plants.
Frontiers in Pharmacology
June 27, 2022
Snehal Bhatt, Maya Armstrong, Tassy Parker et al.
4 citations
Post-traumatic stress disorder (PTSD) and substance use disorders (SUDs) frequently co-occur, a link shaped by adverse childhood experiences, historical and multi-generational traumas, and social, cultural, and spiritual factors. Current treatments for PTSD are only modestly effective, and more research is needed on interventions for co-occurring PTSD and SUD, including whether to treat them together or sequentially. Interest in psychedelics as a treatment augmentation is reviving, though risks remain. This review covers the history of psychedelic research and practices, examining historical trauma, adverse childhood experiences, PTSD, and SUDs through the lens of New Mexico, a state with large Indigenous and Hispanic populations and high rates of trauma and substance use. Future directions include community-based participatory approaches respectful of Indigenous and minority communities.
Frontiers in Pharmacology
June 3, 2024
Gio Kim, Catherine K. Wang, Lily R. Aleksandrova et al.
3 citations
A systematic review of preclinical studies found that extracts from 19 mushroom species and 7 other fungus species nearly all produced antidepressant-like effects in animal models of depression. The review identified 50 relevant studies, mostly in male rodents, using oral administration in acute or chronic regimens. The most common animal model was unpredictable chronic mild stress, while the tail suspension test and forced swim test were frequently used as antidepressant screens. The review discusses each experiment in detail and evaluates the strengths and weaknesses of the studies, highlighting that the antidepressant potential of mushroom and fungus extracts extends beyond psilocybin-containing species to include both psychedelic and non-psychedelic varieties.
Frontiers in Pharmacology
November 20, 2025
Karolina E. Kolaczynska, Daniel Trachsel, Marius C. Hoener et al.
1 citation
A class of psychedelic compounds called 4-substituted 2,6-dimethoxyphenethylamines and their amphetamine counterparts (Ψ derivatives) were tested for their interactions with monoamine receptors and transporters. These derivatives showed moderate to high affinity and activity at the human 5-HT2A receptor, the primary target for psychedelics, with binding affinities ranging from 8 to 1,600 nM and activation potencies from 32 to 3,400 nM. They acted as partial agonists at this receptor. The phenethylamine derivatives also bound to 5-HT1A and 5-HT2C receptors with moderate affinity, while amphetamine derivatives had weaker affinities. Some Ψ derivatives interacted with TAAR1 and adrenergic receptors. Compared to 2,4,5-trisubstituted derivatives, the 2,4,6-trisubstituted Ψ derivatives were generally less potent at the 5-HT2A receptor but more potent than 3,4,5-trisubstituted derivatives.
Frontiers in Pharmacology
September 17, 2025
Xiao Wang, Lijuan Yan, Jiaying Cai et al.
1 citation
A randomized controlled trial compares the risk of respiratory depression between esketamine-based and fentanyl-based analgesia during liver ablation guided by high-frequency harmonic scalpel. If esketamine shows superior respiratory safety, it could become a viable treatment option.
Frontiers in Pharmacology
June 3, 2026
Burton J. Tabaac, Robin L. Carhart-Harris, Teresa Yung
Three individuals with persistent symptoms after traumatic brain injury or hypoxic-ischemic brain injury completed a six-week protocol combining a participant-directed iboga-containing microdosing regimen (using whole root bark biomass with about 3.845% ibogaine content, yielding an estimated 3.8–38.5 mg/day ibogaine equivalent) with weekly Accelerated Experiential Dynamic Psychotherapy and supportive nutraceuticals. All three showed progressive neurological recovery; two reported complete symptom remission at long-term follow-up. Participants discontinued all prescription medications and reported resolution of headaches, brain fog, fatigue, irritability, and mood swings, with a return to regular activities and renewed enthusiasm. The authors note that the findings do not establish causality or iboga-specific efficacy due to the multimodal intervention and methodological limitations.
Frontiers in Pharmacology
May 26, 2026
Michal Ordak
The psychoactive mushroom Amanita muscaria is increasingly used recreationally and for self-therapy, promoted online for stress reduction, mood improvement, sleep, and pain relief despite limited clinical evidence and known toxicity. This narrative review synthesizes evidence showing rising intentional consumption, varied dosing, and outcomes from mild neurological symptoms to severe intoxication requiring hospitalization. Online narratives and informal harm reduction advice normalize use and may lead to underestimating risks. As a non-synthetic psychoactive substance sold in digital markets, A. muscaria poses regulatory and public health challenges, with no standardized management guidelines or systematic surveillance. Greater awareness of its toxicology, misuse patterns, and emergency care is needed.
Frontiers in Pharmacology
March 16, 2026
Alessandra Linardi, Ariadiny Lima Caetano, Rodrigo Portes Ureshino
Scientific interest in psychedelic substances has revived, offering new perspectives on treating neuropsychiatric and neurological disorders. Psychedelics induce neuroplasticity and alleviate symptoms of depression, anxiety, PTSD, and neurodegenerative diseases like Alzheimer's and Parkinson's. A review of six abused recreational drugs—methamphetamine, cocaine, synthetic cathinones, ketamine, nitrous oxide, and heroin—shows they share convergent neurotoxic mechanisms involving oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. Original research demonstrates that social hierarchy modulates methamphetamine reinforcement in rats and is associated with distinct phosphoproteomic signatures in the nucleus accumbens, with HDAC4 phosphorylation differing between dominant and subordinate rats. A mini-review discusses trace amine-associated receptors, particularly TAAR1, as potential therapeutic targets for anxiety and depression.
Frontiers in Pharmacology
March 11, 2026
Katrin Brache, Mauricio Diazgranados
Neuropsychiatric disorders affect nearly one billion people worldwide, and existing treatments are limited by side effects and variable efficacy. This review of 42 Colombian plant species used in Indigenous and local health systems for conditions overlapping with mental and neurological disorders found that ayahuasca (yagé) was the most frequently reported preparation, while Nicotiana tabacum, Erythroxylum coca, and Aloysia citrodora were the most commonly cited species. Leaves (38%), stems (14%), and roots (13%) were the most used plant parts, prepared as decoctions (21%) and infusions (17%).
Frontiers in Pharmacology
March 4, 2026
Mi Zhou, Y M Qi, Fan Zhou et al.
Adding a moderate dose of esketamine (0.03 mg/kg/h) to patient-controlled intravenous analgesia combined with a preoperative intercostal nerve block significantly reduced acute postoperative pain after thoracoscopic lobectomy, compared to a low dose of esketamine or sufentanil alone. Pain scores on the Numerical Rating Scale were lower at 2, 4, 24, 48, and 72 hours after surgery, and the need for rescue analgesia and opioid consumption decreased. The moderate esketamine group also had less postoperative nausea and vomiting than the sufentanil group. Low-dose esketamine did not improve pain control over sufentanil alone.
Frontiers in Pharmacology
December 4, 2025
Maya Nicolas
Ibogaine, a compound from the Tabernanthe iboga plant, may restore reward-system function across multiple disorders—including addiction, OCD, PTSD, and eating disorders—by upregulating GDNF, modulating glutamate and dopamine signaling, and reopening neuroplasticity. These conditions share disrupted dopaminergic and glutamatergic signaling in mesocorticolimbic circuitry, leading to maladaptive reinforcement and motivational dysregulation. Historical, preclinical, and observational evidence suggests ibogaine acts on underlying reward dysfunction rather than only symptoms. However, safety concerns include hERG channel inhibition, requiring strict medical protocols. This review proposes a unified mechanism but notes the framework requires empirical validation.
Frontiers in Pharmacology
December 1, 2025
Tiejia Jiang, Rui Zhao
Esketamine provides relatively good pain control after surgery and is linked to a lower risk of postpartum depression, but this finding is not stable. In pregnant women over 30, esketamine may increase the risk of dizziness. The study was conducted entirely in China, which limits how broadly the results apply.
Frontiers in Pharmacology
January 1, 2016
Bokor, Petra, Frecska, Ede, Winkelman, Michael
Ayahuasca, an Amazonian psychoactive brew containing β-carboline and tryptamine derivatives, remains central to healing ceremonies among indigenous and mestizo populations in South America and is increasingly used worldwide. A growing number of studies indicate that its psychotherapeutic potential is based largely on strong serotonergic effects, while the sigma-1 receptor agonist effect of its active ingredient dimethyltryptamine may allow scientific verification of the diversity of conditions treated in ethnomedical observations. In appropriate therapeutic or ritual settings with proper preparation, mindset, and integration, ayahuasca has proven effective for treating substance dependence. The article argues that therapeutic effects are best understood from a bio-psycho-socio-spiritual model, and that ayahuasca may act against chronic low-grade inflammation and oxidative stress via the sigma-1 receptor.