Human Laboratory Studies on Cannabinoids and Psychosis.
Mohamed Sherif, Rajiv Radhakrishnan, Deepak Cyril D'Souza, Mohini Ranganathan
Biological Psychiatry April 1, 2016 DOI: 10.1016/j.biopsych.2016.01.011 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Population | Healthy human subjects and individuals with schizophrenia |
| Interventions | cannabinoid agonists phytocannabinoids synthetic cannabinoids |
| Topics | Cannabis |
| Keywords | Cb1r Cannabinoids Cognition Dopamine Gaba Glutamate Laboratory Schizophrenia Cannabinoid psychosis Neurobiological mechanisms Experimental rct studies |
| Citations | 127 |
| Key findings | Cannabinoid agonists produce schizophrenia-like symptoms in healthy subjects and transiently worsen symptoms in schizophrenia patients, with no evidence of beneficial effects. |
Abstract
Some of the most compelling evidence supporting an association between cannabinoid agonists and psychosis comes from controlled laboratory studies in humans. Randomized, double-blind, placebo-controlled, crossover laboratory studies demonstrate that cannabinoid agonists, including phytocannabinoids and synthetic cannabinoids, produce a wide range of positive, negative, and cognitive symptoms and psychophysiologic deficits in healthy human subjects that resemble the phenomenology of schizophrenia. These effects are time locked to drug administration, are dose related, and are transient and rarely necessitate intervention. The magnitude of effects is similar to the effects of ketamine but qualitatively distinct from other psychotomimetic drugs, including ketamine, amphetamine, and salvinorin A. Cannabinoid agonists have also been shown to transiently exacerbate symptoms in individuals with schizophrenia in laboratory studies. Patients with schizophrenia are more vulnerable than healthy control subjects to the acute behavioral and cognitive effects of cannabinoid agonists and experience transient exacerbation of symptoms despite treatment with antipsychotic medications. Furthermore, laboratory studies have failed to demonstrate any "beneficial" effects of cannabinoid agonists in individuals with schizophrenia-challenging the cannabis self-medication hypothesis. Emerging evidence suggests that polymorphisms of several genes related to dopamine metabolism (e.g., COMT, DAT1, and AKT1) may moderate the effects of cannabinoid agonists in laboratory studies. Cannabinoid agonists induce dopamine release, although the magnitude of release does not appear to be commensurate to the magnitude and spectrum of their acute psychotomimetic effects. Interactions between the endocannabinoid, gamma-aminobutyric acid, and glutamate systems and their individual and interactive effects on neural oscillations provide a plausible mechanism underlying the psychotomimetic effects of cannabinoids.
Comparable studies
Other systematic reviews and meta-analyses on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of cannabis use on outcomes of psychotic disorders: systematic review People with psychotic disorders, as examined in 13 longitudinal studies | 2008 | Systematic review | |
| The Impact of Cannabis Use on Cognitive Functioning in Patients With Schizophrenia: A Meta-analysis of Existing Findings and New Data in a First-Episode Sample Patients with established schizophrenia (meta-analysis: 572) and patients with... | 2010 | Meta-analysis and cross-sectional observational study | n = 700 |
| Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review | 2020 | Systematic review | |
| Neuroimaging in cannabis use: a systematic review of the literature Cannabis users and controls in neuroimaging studies | 2009 | Systematic review | |
| Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties | 2020 | Systematic review |
Citations in the library
Cited by 31
- Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males Translational Psychiatry November 29, 2016
- Subcortical Local Functional Hyperconnectivity in Cannabis Dependence Biological Psychiatry: Cognitive Neuroscience and Neuroimaging November 23, 2017
- Exposure to cannabinoids can lead to persistent cognitive and psychiatric disorders European Journal of Pain February 22, 2019
- “Hallucinations” Following Acute Cannabis Dosing: A Case Report and Comparison to Other Hallucinogenic Drugs Cannabis and Cannabinoid Research April 2, 2018
- Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research Frontiers in Pharmacology June 21, 2017
and 26 more in the library
Cites 46
- Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Journal of Psychopharmacology October 5, 2012
- Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Archives of General Psychiatry 2009
- Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine Archives of General Psychiatry September 1, 2005
- Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Archives of General Psychiatry April 1, 2009
- Modulation of effective connectivity during emotional processing by Δ9-tetrahydrocannabinol and cannabidiol The International Journal of Neuropsychopharmacology September 24, 2009
and 41 more in the library