Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia.
Matthijs G. Bossong, Raymond J.m. Niesink
Progress in Neurobiology November 2010 DOI: 10.1016/j.pneurobio.2010.06.010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Cannabis |
| Key findings | Proposes that adolescent THC exposure distorts normal late postnatal brain maturation by disturbing glutamatergic transmission, potentially leading to schizophrenia; the model provides testable hypotheses for future studies. |
Abstract
Cannabis use during adolescence increases the risk of developing psychotic disorders later in life. However, the neurobiological processes underlying this relationship are unknown. This review reports the results of a literature search comprising various neurobiological disciplines, ultimately converging into a model that might explain the neurobiology of cannabis-induced schizophrenia. The article briefly reviews current insights into brain development during adolescence. In particular, the role of the excitatory neurotransmitter glutamate in experience-dependent maturation of specific cortical circuitries is examined. The review also covers recent hypotheses regarding disturbances in strengthening and pruning of synaptic connections in the prefrontal cortex, and the link with latent psychotic disorders. In the present model, cannabis-induced schizophrenia is considered to be a distortion of normal late postnatal brain maturation. Distortion of glutamatergic transmission during critical periods may disturb prefrontal neurocircuitry in specific brain areas. Our model postulates that adolescent exposure to Δ9-tetrahydrocannabinol (THC), the primary psychoactive substance in cannabis, transiently disturbs physiological control of the endogenous cannabinoid system over glutamate and GABA release. As a result, THC may adversely affect adolescent experience-dependent maturation of neural circuitries within prefrontal cortical areas. Depending on dose, exact time window and duration of exposure, this may ultimately lead to the development of psychosis or schizophrenia. The proposed model provides testable hypotheses which can be addressed in future studies, including animal experiments, reanalysis of existing epidemiological data, and prospective epidemiological studies in which the role of the dose-time-effect relationship should be central.
Comparable studies
Other narrative reviews on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Causal association between cannabis and psychosis: examination of the evidence | 2004 | Review | |
| Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history. General (historical and pharmacological review) | 2018 | Review | |
| Psychiatric effects of cannabis | 2001 | Review | |
| Beyond THC: The New Generation of Cannabinoid Designer Drugs | 2011 | Review | |
| Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug | 2006 | Review |
Citations in the library
Cited by 46
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- The neuropsychopharmacology of cannabis: A review of human imaging studies Pharmacology & Therapeutics October 20, 2018
- Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males Translational Psychiatry November 29, 2016
- Cannabis use and cognitive dysfunction Indian Journal of Psychiatry 2011
- Cannabis use and vulnerability for psychosis in early adolescence—a TRAILS study Addiction December 10, 2012
and 41 more in the library
Cites 13
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Recent advances in the phencyclidine model of schizophrenia American Journal of Psychiatry October 1, 1991
- Causal association between cannabis and psychosis: examination of the evidence The British Journal of Psychiatry January 30, 2004
- High-potency cannabis and the risk of psychosis The British Journal of Psychiatry November 30, 2009
- Abstinent adolescent marijuana users show altered fMRI response during spatial working memory. Psychiatry Research May 30, 2008
and 8 more in the library