Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers
J. Hirvonen, R. Goodwin, Cheng-Ta Li, Garth E Terry, Sami S Zoghbi, Cheryl L. Morse, Victor W Pike, Nora D. Volkow, Marilyn A. Huestis, Robert B Innis
Molecular Psychiatry July 12, 2011 DOI: 10.1038/mp.2011.82 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Human subjects who chronically smoke cannabis and controls |
| Duration | ~4 weeks of monitored abstinence |
| Topics | Cannabis |
| Key findings | Chronic cannabis smokers showed reversible and regionally selective downregulation of cortical CB1 receptors, which correlated with years of smoking and normalized after ~4 weeks of abstinence. The authors argue this neuroadaptation may promote cannabis dependence. |
Abstract
Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB1 (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in human subjects who chronically smoke cannabis. Downregulation correlated with years of cannabis smoking and was selective to cortical brain regions. After ∼4 weeks of continuously monitored abstinence from cannabis on a secure research unit, CB1 receptor density returned to normal levels. This is the first direct demonstration of cortical cannabinoid CB1 receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain.
Comparable studies
Other observational and cohort studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population | 2009 | Case-control study | n = 454 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline | 2011 | Observational cohort | n = 1,923 |
| Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... | 2005 | Observational cohort | n = 535 |
Citations in the library
Cited by 86
- The neuropsychopharmacology of cannabis: A review of human imaging studies Pharmacology & Therapeutics October 20, 2018
- Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis ‘amotivational’ hypotheses Psychopharmacology September 2, 2016
- Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males Translational Psychiatry November 29, 2016
- Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity Journal of Psychopharmacology April 23, 2019
- Shifted balance of dorsal versus ventral striatal communication with frontal reward and regulatory regions in cannabis‐dependent males Human Brain Mapping September 12, 2018
and 81 more in the library
Cites 7
- Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users. Journal of Psychopharmacology May 2009
- Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis. Neuropsychopharmacology September 2008
- Cannabis reinforcement and dependence: role of the cannabinoid CB1 receptor. Addiction Biology June 2008
- Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users. Psychopharmacology November 2007
- Regulation of cannabinoid CB1 receptors in the central nervous system by chronic cannabinoids. Critical reviews in neurobiology 2003
and 2 more in the library