Combination Chemistry: Structure-Activity Relationships of Novel Psychoactive Cannabinoids.
Jenny L Wiley, Julie A. Marusich, Brian F Thomas
Current Topics in Behavioral Neurosciences 2017 DOI: 10.1007/7854_2016_17 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Cannabis |
| Keywords | Indoles Jwh-018 Receptor binding Synthetic cannabinoids |
| Key findings | The chapter argues that synthetic cannabinoids, despite evolving structures from JWH-018 to indazole-derived compounds like AB-PINACA and AB-CHMINACA, share high CB1 receptor affinity and, when tested, often show greater CB1 efficacy and in vivo potency than THC, producing a characteristic mouse effect profile; thermolysis and uncertain purity may yield degradants and unpredictable, sometimes harmful effects in users. |
Abstract
Originally developed as research tools for use in structure-activity relationship studies, synthetic cannabinoids contributed to significant scientific advances in the cannabinoid field. Unfortunately, a subset of these compounds was diverted for recreational use beginning in the early 2000s. As these compounds were banned, they were replaced with additional synthetic cannabinoids with increasingly diverse chemical structures. This chapter focuses on integration of recent results with those covered in previous reviews. Whereas most of the early compounds were derived from the prototypic naphthoylindole JWH-018, currently popular synthetic cannabinoids include tetramethylcyclopropyl ketones and indazole-derived cannabinoids (e.g., AB-PINACA, AB-CHMINACA). Despite their structural differences, psychoactive synthetic cannabinoids bind with high affinity to CB1 receptors in the brain and, when tested, have been shown to activate these receptors and to produce a characteristic profile of effects, including suppression of locomotor activity, antinociception, hypothermia, and catalepsy, as well as Δ9-tetrahydrocannabinol (THC)-like discriminative stimulus effects in mice. When they have been tested, synthetic cannabinoids are often found to be more efficacious at activation of the CB1 receptor and more potent in vivo. Further, their chemical alteration by thermolysis during use and their uncertain stability and purity may result in exposure to degradants that differ from the parent compound contained in the original product. Consequently, while their intoxicant effects may be similar to those of THC, use of synthetic cannabinoids may be accompanied by unpredicted, and sometimes harmful, effects.
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 2
Cites 9
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- Withdrawal phenomena and dependence syndrome after the consumption of "spice gold". Deutsches Arzteblatt international July 3, 2009
- Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond. Addiction Biology June 2008
and 4 more in the library