Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond.
Roger G Pertwee
Addiction Biology June 2008 DOI: 10.1111/j.1369-1600.2008.00108.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Cannabis |
| Key findings | The review reports that delta-9-THC acts through at least two cannabinoid receptors, CB1 and CB2, and that mammalian tissues release endocannabinoids such as anandamide and 2-arachidonoylglycerol that appear to maintain central nervous system homeostasis and may oppose, mediate, or exacerbate certain disorders. It describes actual and potential clinical uses for cannabinoid receptor agonists and antagonists and for compounds that indirectly affect receptor activation, including inhibitors of endocannabinoid hydrolysis. |
Abstract
A major finding--that (-)-trans-Delta(9)-tetrahydrocannabinol (Delta(9)-THC) is largely responsible for the psychotropic effects of cannabis--prompted research in the 1970s and 1980s that led to the discovery that this plant cannabinoid acts through at least two types of cannabinoid receptor, CB(1) and CB(2), and that Delta(9)-THC and other compounds that target either or both of these receptors as agonists or antagonists have important therapeutic applications. It also led to the discovery that mammalian tissues can themselves synthesize and release agonists for cannabinoid receptors, the first of these to be discovered being arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol. These 'endocannabinoids' are released onto their receptors in a manner that appears to maintain homeostasis within the central nervous system and sometimes either to oppose or to mediate or exacerbate the unwanted effects of certain disorders. This review provides an overview of the pharmacology of cannabinoid receptors and their ligands. It also describes actual and potential clinical uses both for cannabinoid receptor agonists and antagonists and for compounds that affect the activation of cannabinoid receptors less directly, for example by inhibiting the enzymatic hydrolysis of endocannabinoids following their release.
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 17
- Baths Salts, Spice, and Related Designer Drugs: The Science Behind the Headlines Journal of Neuroscience November 12, 2014
- Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data? Pharmacology & Therapeutics February 1, 2018
- Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis Psychopharmacology October 13, 2022
- A Comparative Review of the Neuro-Psychopharmacology of Hallucinogen-Induced Altered States of Consciousness: The Uniqueness of Some Hallucinogens NeuroQuantology June 1, 2012
- Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects ofδ-9-THC Psychological Medicine March 5, 2018
and 12 more in the library
Cites 4
- The psychoactive plant cannabinoid, Delta9-tetrahydrocannabinol, is antagonized by Delta8- and Delta9-tetrahydrocannabivarin in mice in vivo. British Journal of Pharmacology March 2007
- Regulation of cannabinoid CB1 receptors in the central nervous system by chronic cannabinoids. Critical reviews in neurobiology 2003
- Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proceedings of the National Academy of Sciences of the United States of America July 31, 2001
- Cannabinoid receptor localization in brain. Proceedings of the National Academy of Sciences March 1990