Disruption of hippocampal synaptic transmission and long‐term potentiation by psychoactive synthetic cannabinoid ‘Spice’ compounds: comparison with Δ9‐tetrahydrocannabinol
Alexander F. Hoffman, Matthew D. Lycas, Jakub Kaczmarzyk, Charles E. Spivak, Michael H. Baumann, Carl R. Lupica
Addiction Biology January 5, 2016 DOI: 10.1111/adb.12334 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mouse hippocampal slices |
| Intervention | AM2201 |
| Topics | Cannabis |
| Keywords | Synthetic cannabinoids Am251 Cannabinoid receptor Long-term potentiation Pharmacology Neurotransmission Hippocampal formation Inverse agonist Hippocampus Biochemistry |
| Citations | 39 |
| Key findings | Synthetic cannabinoids JWH-018, AM2201, and XLR-11 activate CB1 receptors in the mouse hippocampus, inhibiting synaptic transmission and impairing long-term potentiation, with JWH-018 showing the highest potency. |
Abstract
Abstract There has been a marked increase in the availability of synthetic drugs designed to mimic the effects of marijuana. These cannabimimetic drugs, sold illicitly as ‘Spice’ and related products, are associated with serious medical complications in some users. In vitro studies suggest that synthetic cannabinoids in these preparations are potent agonists at central cannabinoid CB1 receptors (CB1Rs), but few investigations have delineated their cellular effects, particularly in comparison with the psychoactive component of marijuana, Δ 9 ‐tetrahydrocannabinol (Δ 9 ‐THC). We compared the ability of three widely abused synthetic cannabinoids and Δ 9 ‐THC to alter glutamate release and long‐term potentiation in the mouse hippocampus. JWH‐018 was the most potent inhibitor of hippocampal synaptic transmission (EC 50 ~15 nM), whereas its fluoropentyl derivative, AM2201, inhibited synaptic transmission with slightly lower potency (EC 50 ~60 nM). The newer synthetic cannabinoid, XLR‐11, displayed much lower potency (EC 50 ~900 nM) that was similar to Δ 9 ‐THC (EC 50 ~700 nM). The effects of all compounds occurred via activation of CB1Rs, as demonstrated by reversal with the selective antagonist/inverse agonist AM251 or the neutral CB1R antagonist PIMSR1. Moreover, AM2201 was without effect in the hippocampus of transgenic mice lacking the CB1R. Hippocampal slices exposed to either synthetic cannabinoids or Δ 9 ‐THC exhibited significantly impaired long‐term potentiation (LTP). We find that, compared with Δ 9 ‐THC, the first‐generation cannabinoids found in Spice preparations display higher potency, whereas a recent synthetic cannabinoid is roughly equipotent with Δ 9 ‐THC. The disruption of synaptic function by these synthetic cannabinoids is likely to lead to profound impairments in cognitive and behavioral function.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 10
- Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data? Pharmacology & Therapeutics February 1, 2018
- Positive Allosteric Modulation of the 5-HT1A Receptor by Indole-Based Synthetic Cannabinoids Abused by Humans ACS Chemical Neuroscience April 23, 2020
- Subtle Structural Modification of a Synthetic Cannabinoid Receptor Agonist Drastically Increases its Efficacy at the CB1 Receptor ACS Chemical Neuroscience October 17, 2023
- Cognitive dysfunction and impaired neuroplasticity following repeated exposure to the synthetic cannabinoid JWH-018 in male mice. British Journal of Pharmacology July 13, 2023
- Effect of Cannabis on Memory Consolidation, Learning and Retrieval and Its Current Legal Status in India: A Review. Biomolecules January 12, 2023
and 5 more in the library
Cites 9
- Baths Salts, Spice, and Related Designer Drugs: The Science Behind the Headlines Journal of Neuroscience November 12, 2014
- Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug and Alcohol Dependence November 1, 2014
- Cross-substitution of Δ9-tetrahydrocannabinol and JWH-018 in drug discrimination in rats. Pharmacology, Biochemistry, and Behavior September 2014
- Cannabinoids in disguise: Δ9-tetrahydrocannabinol-like effects of tetramethylcyclopropyl ketone indoles. Neuropharmacology December 2013
- Designer drugs: a medicinal chemistry perspective. Annals of the New York Academy of Sciences February 2012
and 4 more in the library