Zenodo (CERN European Organization for Nuclear Research) • July 1, 2026 • Schüller Thomas
Mescaline is the only phenethylamine among the classic psychedelics, with the lowest affinity for the 5-HT2A receptor, requiring the highest doses (hundreds of milligrams) and producing a dose-dependent duration of 6.4 to 14 hours. Clinical research is the weakest strand: as of 2026, no adequate randomized controlled trial exists. In the ecologically bound case of peyote, the logic of dispossession reverses compared to synthetic substances like LSD and psilocybin. The work elevates Discipline 8 (Law/Society) to address peyote conservation (IUCN 'vulnerable') and Indigenous rights (Native American Church, AIRFA 1994) as a standalone discipline.
Journal of psychopharmacology (Oxford, England) • June 25, 2026 • Pavan S Brar, Rebecca B Price, Stephen Ross et al.
Psychedelic compounds like psilocybin and LSD are being studied again as potential treatments, but research usually excludes people at risk for psychosis. This narrative review examines the historical and theoretical links between psychedelics and schizophrenia spectrum disorders (SSDs), including the psychotomimetic hypothesis. The authors compare the phenomenological experiences induced by psychedelics with those of SSDs, finding both overlap and important qualitative differences that challenge a simple equivalence. They review neural mechanisms involving serotonin, dopamine, and glutamate. Clinical evidence shows psychedelics can worsen existing psychotic illness and may trigger psychosis in vulnerable individuals, though the risk magnitude is not well quantified. The authors suggest potential therapeutic applications for carefully selected symptoms in stable patients using low-dose, controlled approaches and provide recommendations for managing psychosis-related risk.
Addictive behaviors • June 1, 2026 • Sebastian Ehmann, Nathan M Hager, Paul S Regier et al.
Using data from the 2023 U.S. National Survey on Drug Use and Health, lifetime use of mescaline or peyote was associated with lower opioid use disorder severity, while lifetime use of LSD, psilocybin, MDMA, or DMT was associated with higher severity. The link between mescaline/peyote use and lower severity appeared only among adults with high mental health impairment. The findings suggest that different types of psychedelic use have divergent relationships with opioid use disorder severity, and that mental health status may influence these associations.
Neuroscience bulletin • May 21, 2026 • Noah Cavallaro, Priya Rai, David Akins et al.
Mescaline, a psychedelic used ceremonially for thousands of years, produces distinct brain effects that differ from LSD and psilocybin. In awake rats, mescaline suppressed BOLD signal in the cerebellum, suggesting it disconnects this region from forebrain areas. However, resting-state scans showed the cerebellum became hyperconnected to the hippocampus, thalamus, somatosensory cortex, and midbrain. Mescaline also eliminated normal brain responses to rewarding smells, indicating disrupted sensory processing. Acoustic startle tests revealed frequency-dependent effects: enhancement at 4 kHz (+27.6%) and 20 kHz (+27.3%), but impairment at 12 kHz (-16.4%). The cerebellum may act as a dysregulated sensory filter, flooding forebrain circuits with unprocessed information, potentially explaining psychedelic-induced perceptual changes.
Fa yi xue za zhi • April 25, 2026 • Ruidi Shen, Zhenhua Qian
Abuse of mescaline and its analogues, a class of phenethylamine compounds often overlooked, has gradually increased worldwide. This review covers their basic information, pharmacological and toxicological properties, and detection methods, aiming to guide future research and provide references for forensic examination involving these substances.
Neuropharmacology • May 1, 2020 • Adam L Halberstadt, Muhammad Chatha, Adam K Klein et al. • 274 citations
Serotonergic hallucinogens like LSD cause head twitches in rodents through 5-HT2A receptor activation. This study tested whether the potency of hallucinogens in the mouse head-twitch response (HTR) paradigm correlates with their potencies in rats and humans. Dose-response experiments with phenylalkylamine and tryptamine hallucinogens in C57BL/6J mice expanded HTR potency data to 41 compounds. For 36 agents with human data, a strong positive correlation (r = 0.9448) was found between mouse HTR potencies and human hallucinogenic potencies. HTR potencies also correlated with drug discrimination ED50 values in rats trained with LSD (r = 0.9484, n = 16) or 2,5-dimethoxy-4-methylamphetamine (r = 0.9564, n = 21). These three behavioral effects show consistent potencies linked to 5-HT2A receptor activation, supporting the HTR assay as a predictive preclinical model for hallucinogen potency in humans.
Current topics in behavioral neurosciences • January 1, 2017 • Juan F. López‐giménez, Javier González‐maeso • 302 citations
Hallucinogens such as mescaline, psilocybin, and LSD profoundly alter consciousness, emotion, and cognition. Their discovery, particularly LSD's similarity to serotonin, suggested that biogenic amines like serotonin are involved in mental disorders such as schizophrenia. Although hallucinogens bind to multiple G protein-coupled receptor subtypes, their key effects involve agonist activity at the serotonin 5-HT2A receptor. This chapter reviews recent advances in understanding hallucinogen action by characterizing the structure, neuroanatomical location, and function of the 5-HT2A receptor.
Journal of Psychopharmacology • March 1, 2015 • Pål-ørjan Johansen, Teri Suzanne Krebs • 300 citations
A large study of 135,095 randomly selected US adults, including 19,299 who had used psychedelics such as LSD, psilocybin, or mescaline, found no link between lifetime psychedelic use and mental health problems. After adjusting for sociodemographics, other drug use, and childhood depression, there were no significant associations with past-year serious psychological distress, mental health treatment, suicidal thoughts, plans, or attempts, depression, or anxiety. Psychedelic use was not an independent risk factor for mental health issues. Serious adverse events are extremely rare, and psychedelics are not known to harm organs or cause addiction. The authors argue that prohibiting psychedelics as a public health measure is difficult to justify.
PLoS ONE • August 19, 2013 • Teri Suzanne Krebs, Pål-ørjan Johansen • 338 citations
Lifetime use of classical serotonergic psychedelics (LSD, psilocybin, mescaline) is not associated with an increased risk of mental health problems. Analyzing data from over 130,000 US adults, researchers found no significant link between psychedelic use and higher rates of serious psychological distress, mental health treatment, or specific psychiatric disorders including panic disorder, major depression, mania, social phobia, and PTSD. In some cases, psychedelic use correlated with lower rates of mental health issues. The findings suggest that psychedelics are not an independent risk factor for mental health problems.
Biological psychiatry • October 15, 2005 • John H Halpern, Andrea R Sherwood, James I Hudson et al. • 186 citations
Regular use of peyote, a hallucinogen-containing cactus, in a religious setting among Navajo Native Americans does not appear to cause long-term psychological or cognitive deficits. In a study comparing three groups—61 Native American Church members who regularly ingested peyote, 36 individuals with past alcohol dependence who had been sober for at least two months, and 79 individuals with minimal substance use—the peyote group showed no significant differences on a mental health inventory or ten neuropsychological tests compared to the minimal-use group. In contrast, the former alcoholic group showed significant deficits on all mental health scales and two neuropsychological measures. Total lifetime peyote use was not linked to worse performance. These findings may not apply to illicit hallucinogen users.