New Paradigms of Old Psychedelics in Schizophrenia
Danish Mahmood, Sattam Khulaif Alenezi, Md Jamir Anwar, Faizul Azam, Kamal A. Qureshi, Mariusz Jaremko
Pharmaceuticals May 23, 2022 DOI: 10.3390/ph15050640 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Anxiety LSD Mescaline Psilocybin Serotonin |
| Keywords | Hallucinogen Schizophrenia object-oriented programming 5-HT Receptor |
| Citations | 29 |
| Key findings | Psychedelics activate serotonin 5-HT2A receptors and may share a common pathway with atypical antipsychotics through serotonin–glutamate receptor interactions, suggesting brain resetting mechanisms as a therapeutic basis. |
Abstract
Psychedelics such as lysergic acid diethylamide (LSD), psilocybin (magic mushrooms), and mescaline exhibit intense effects on the human brain and behaviour. In recent years, there has been a surge in studies investigating these drugs because clinical studies have shown that these once banned drugs are well tolerated and efficacious in medically supervised low doses called microdosing. Psychedelics have demonstrated efficacy in treating neuropsychiatric maladies such as difficult to treat anxiety, depression, mood disorders, obsessive compulsive disorders, suicidal ideation, posttraumatic stress disorder, and also in treating substance use disorders. The primary mode of action of psychedelics is activation of serotonin 5-HT2A receptors affecting cognition and brain connectivity through the modulation of several downstream signalling pathways via complex molecular mechanisms. Some atypical antipsychotic drugs (APDs) primarily exhibit pharmacological actions through 5-HT2A receptors, which are also the target of psychedelic drugs. Psychedelic drugs including the newer second generation along with the glutamatergic APDs are thought to mediate pharmacological actions through a common pathway, i.e., a complex serotonin–glutamate receptor interaction in cortical neurons of pyramidal origin. Furthermore, psychedelic drugs have been reported to act via a complex interplay between 5HT2A, mGlu2/3, and NMDA receptors to mediate neurobehavioral and pharmacological actions. Findings from recent studies have suggested that serotoninergic and glutamatergic neurotransmissions are very closely connected in producing pharmacological responses to psychedelics and antipsychotic medication. Emerging hypotheses suggest that psychedelics work through brain resetting mechanisms. Hence, there is a need to dig deeply into psychedelic neurobiology to uncover how psychedelics could best be used as scientific tools to benefit psychiatric disorders including schizophrenia.
Comparable studies
Other narrative reviews on LSD for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Modern Clinical Research on LSD | 2017 | Review | |
| Ayahuasca: Pharmacology, neuroscience and therapeutic potential | 2016 | Review | |
| Psychedelic Drugs in Biomedicine | 2017 | Review | |
| Studies on Lysergic Acid Diethylamide (LSD-25) Nonpsychotic subjects | 1956 | Review | |
| The Past and Future of Psychedelic Science: An Introduction to This Issue | 2019 | Review |
Citations in the library
Cited by 17
- Expert Opinion on Psychedelic-Assisted Psychotherapy for People with Psychopathological Psychotic Experiences and Psychotic Disorders International Journal of Mental Health and Addiction April 1, 2024
- Psychedelics for alzheimer's disease-related dementia: Unveiling therapeutic possibilities and pathways Ageing Research Reviews February 1, 2024
- Therapeutic modulation of the kynurenine pathway in severe mental illness and comorbidities: A potential role for serotonergic psychedelics. Progress in Neuro-Psychopharmacology and Biological Psychiatry August 30, 2024
- Molecular and Medical Aspects of Psychedelics International Journal of Molecular Sciences December 23, 2023
- Psychedelics in the Treatment of Neurologic and Psychiatric Disorders: Coincidence or a New Point of View. Molecular Neurobiology June 4, 2025
and 12 more in the library
Cites 78
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
and 73 more in the library