Neurometabolic Effects of Psilocybin, 3,4-Methylenedioxyethylamphetamine (MDE) and d-Methamphetamine in Healthy Volunteers A Double-Blind, Placebo-Controlled PET Study with [18F]FDG
Neuropsychopharmacology June 1, 1999 DOI: 10.1016/s0893-133x(98)00089-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled human FDG-PET study Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Healthy human subjects |
| Interventions | Psilocybin 3 4-methylenedioxyethylamphetamine (MDE) d-methamphetamine |
| Dose | 0.2 mg/kg psilocybin, 2 mg/kg MDE, 0.2-0.4 mg/kg methamphetamine |
| Duration | Two scans within 2-4 weeks |
| Topics | Psilocybin |
| Keywords | Placebo Methamphetamine Psychopharmacology Hallucinogen Anesthesia |
| Citations | 224 |
| Key points | Psilocybin increased right frontotemporal cortical metabolism and decreased thalamic metabolism, while MDE and methamphetamine induced cortical hypometabolism and cerebellar hypermetabolism, and all three substances attenuated cognitive activation-related increases in left frontocortical regions. |
Abstract
The neurometabolic effects of the hallucinogen psilocybin (PSI; 0.2 mg/kg), the entactogen 3,4-methylenedioxyethylamphetamine (MDE; 2 mg/kg) and the stimulant d-methamphetamine (METH; 0.2-0.4 mg/kg) and the drugs' interactions with a prefrontal activation task were investigated in a double-blind, placebo-controlled human [F-18]fluorodeoxyglucoseFDG-positron emission tomographicPET study (each group: n = 8). Subjects underwent two scans (control: word repetition; activation word association) within 2-4 weeks. Psilocybin increased rMRGlu in distinct right hemispheric frontotemporal cortical regions, particularly in the anterior cingulate and decreased rMRGlu in the thalamus. Both MDE and METH induced cortical hypometabolism and cerebellar hypermetabolism. In the MDE group, cortical hypometabolism was more pronounced in frontal regions, with the exception of the right anterior cingulate, which tended to be hyperactive. Cognitive activation-related increases in left frontocortical regions were attenuated under all three psychoactive substances, but less so under MDE. Taking into account performance data and subjective reports on task difficulty, these effects may result from different mechanisms across the three groups. Our PSI data are in line with studies on acute schizophrenic patients suggesting frontal overactivity at rest, but diminished capacity to activate prefrontal regions upon cognitive demand. The MDE data support the hypothesis that entactogens constitute a distinct psychoactive substance class, which takes an intermediate position between stimulants and hallucinogens.
Comparable studies
Other randomized controlled trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety | 2016 | Randomized controlled trial | n = 51 |
| Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression | 2016 | Double-blind, placebo-controlled, crossover trial | n = 29 |
| Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... | 2006 | Double-blind study | n = 36 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
Citations in the library
Cited by 147
- Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases The Journal of Nervous and Mental Disease March 4, 2014
- Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies Journal of Psychopharmacology September 20, 2010
- Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacology & Therapeutics May 1, 2019
- The pharmacology of psilocybin Addiction Biology October 1, 2002
- The Pharmacology of Lysergic Acid Diethylamide: A Review CNS Neuroscience & Therapeutics November 11, 2008
and 142 more in the library
Cites 9
- Differences Between the Mechanism of Action of MDMA, MBDB, and the Classic Hallucinogens. Identification of a New Therapeutic Class: Entactogens Journal of Psychoactive Drugs October 1, 1986
- Dose-Response Study of N,N-Dimethyltryptamine in Humans Archives of General Psychiatry February 1, 1994
- Ketamine activates psychosis and alters limbic blood flow in schizophrenia Neuroreport April 1, 1995
- Recreational MDMA use in Sydney: a profile of ‘Ecstasy’ users and their experiences with the drug British Journal of Addiction August 1, 1992
- Mescaline-induced psychopathological, neuropsychological, and neurometabolic effects in normal subjects: experimental psychosis as a tool for psychiatric research. Biological Psychiatry December 1, 1992
and 4 more in the library