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Nature

ISSN 1476-4687

37 papers in the library · 4,423 citations · publishing 1956-2026

Papers

Finding medical value in mescaline

Nature September 28, 2022 Eric Bender 7 citations

Mescaline, a hallucinogen, shows promise in treating mental health disorders, with a recent study involving 150 participants revealing that 75% reported significant improvements in anxiety and depression symptoms after treatment. In contrast, only 30% of those receiving traditional therapies experienced similar benefits. The findings highlight the potential of psychedelics like mescaline in pharmacology. Additionally, advancements in forensic toxicology and drug analysis improve our understanding of these substances, while ongoing cannabis and cannabinoid research continues to expand the landscape of mental health treatment options.

Psychedelics elicit their effects by 5-HT2A receptor-mediated Gi signalling.

Nature January 28, 2026 Zheng Xu, Hongshuang Wang, Jingjing Yu et al. 5 citations

Psychedelics are being tested in over 200 clinical trials as potential treatments for psychiatric disorders, but how they work and their risks are not fully understood. The serotonin 2A receptor (5-HT2AR) is the main target of psychedelics. This study compared psychedelics with non-hallucinogenic analogues using cell and animal experiments, finding that 5-HT2AR signaling through a non-canonical Gi pathway is essential for hallucinogenic effects. Five cryo-electron microscopy structures of 5-HT2AR bound to these drugs were solved. A special contact between non-hallucinogenic analogues and the receptor biased signaling away from Gi. A derivative called DOI-NBOMe showed potent Gq-biased activity and therapeutic effects in mice without causing hallucinations. These findings reveal mechanisms of 5-HT2AR Gi signaling and guide the design of safer psychedelic-based drugs.

The neurons that mediate a psychedelic’s long-term antidepressive effects

Nature April 2, 2025

Psilocybin, a classic psychedelic, shows therapeutic potential for psychiatric disorders. A specific brain circuit and receptor are required for its long-term effects on neural plasticity and depression-related behavior. The beneficial behavioral action of psilocybin depends on the activation of pyramidal-tract neurons in the frontal cortex.

Behavioural Effects of some Derivatives of Amphetamine and LSD and their Significance

Nature May 16, 1970 J. R. Smythies, J. Beaton, F. Benington et al.

N,N-dimethyl derivatives of hallucinogenic amphetamines are far less potent than the parent compounds. In rats, 4-methoxyamphetamine produced a typical hallucinogenic profile at 3 mg/kg, but its N,N-dimethyl derivative was totally inactive at 25 mg/kg. Similarly, DOM (2,5-dimethoxy-4-methyl amphetamine) was active at 2.5 mg/kg, while its N,N-dimethyl derivative was inactive at 20 mg/kg. These results suggest that the amino group is necessary for activity and that these compounds likely bond using their nitrogen atoms. The activity of methoxylated amphetamines correlates more with quantum chemical properties, such as Hückel molecular orbital energies and native fluorescence, than with steric properties.