Studies with psychedelic drugs in human volunteers
Abstract
Scientific curiosity and fascination have played a key role in human research with psychedelics along with the hope that perceptual alterations and heightened insight could benefit well-being and play a role in the treatment of various neuropsychiatric disorders. These motivations need to be tempered by a realistic assessment of the hurdles to be cleared for therapeutic use. Development of a psychedelic drug for treatment of a serious psychiatric disorder presents substantial although not insurmountable challenges. While the varied psychedelic agents described in this chapter share some properties, they have a range of pharmacologic effects that are reflected in the gradation in intensity of hallucinogenic effects from the classical agents to DMT, MDMA, ketamine, dextromethorphan and new drugs with activity in the serotonergic system. The common link seems to be serotonergic effects modulated by NMDA and other neurotransmitter effects. The range of hallucinogens suggest that they are distinct pharmacologic agents and will not be equally safe or effective in therapeutic targets. Newly synthesized specific and selective agents modeled on the legacy agents may be worth considering. Defining therapeutic targets that represent unmet medical need, addressing market and commercial issues, and finding treatment settings to safely test and use such drugs make the human testing of psychedelics not only interesting but also very challenging. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.
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Little evidence exists to assess the range of psychedelic effects, safety considerations, and applicability of treatment for patients with personality disorders.
“Little evidence exists to assess the range of psychedelic effects, safety considerations, and applicability of treatment for these patients (12, 13).”
From Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach (2025) · cites this paper as [13]
Most clinical studies on PAT have explicitly excluded individuals with personality disorders.
“However, the potential for psychedelics to treat personality disorders remains unclear, as most clinical studies on PAT have explicitly excluded individuals with these conditions.”
From Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach (2025) · cites this paper as [13]
A scientific gap exists around the potential for psychedelic therapies to treat personality disorders.
“Thus, a scientific gap exists around the potential for psychedelic therapies to treat personality disorders.”
From Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach (2025) · cites this paper as [13]
Comorbid conditions such as suicidality and substance use disorders further complicate research efforts in personality disorder populations.
“Moreover, comorbid conditions such as suicidality and substance use disorders further complicate research efforts (13, 18, 20, 21).”
From Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach (2025) · cites this paper as [13]
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Psychedelics and Psychedelic-Assisted Psychotherapy
Reiff, C. M., Richman, E. E., Nemeroff, C. B., Carpenter, L. L., Widge, A. S., Rodríguez, C. I., Kalin, N. H., & McDonald, W. M. (2021) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.19104 · Cited by 21 · see citing works
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A Systematic Study of Microdosing PsychedelicsPreprint
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- Authors
- Sellers, E. M., Romach, M. K., & Leiderman, D. B.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Sellers, Edward.M.
- ORCID
- Sellers, Edward.M.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 142
- Pages
- 116-134
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2769124319
- Cited by
- 42
- References
- 142
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 5 · 2023: 8 · 2022: 6 · 2021: 6 · 2020: 1 · 2019: 2 · 2018: 5
- FWCI
- 0.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Keywords
- psychedelics, hallucinogens, serotonergic system, NMDA receptor modulation, MDMA, ketamine, dextromethorphan, DMT, classical psychedelics, mental illness, therapeutic target, drug safety and efficacy
- MeSH terms
- Hallucinogens, Humans, Biomedical Research, Healthy Volunteers
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