Evaluation of agonist-antagonist properties of nitrogen mustard and cyano derivatives of delta 8-tetrahydrocannabinol.
J L Wiley, D R Compton, P M Gordon, C Siegel, M Singer, A Dutta, Aron H Lichtman, R L Balster, R K Razdan, B R Martin
Neuropharmacology 1996 DOI: 10.1016/s0028-3908(96)00120-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Mice and rats |
| Interventions | NM-delta 8-THC CY-delta 8-THC delta 9-THC CP 55 940 |
| Topics | Cannabis |
| Key points | Both synthesized analogs bound brain cannabinoid receptors and produced delta 9-THC-like acute effects in mice (locomotor suppression, hypothermia, antinociception, catalepsy). Apparent attenuation of delta 9-THC effects was confounded by acute tolerance. NM-delta 8-THC, but not CY-delta 8-THC, attenuated CP 55,940's discriminative stimulus effects in rats days after injection, suggesting adding a nitrogen group does not eliminate agonist effects and may yield delayed attenuation. |
Abstract
delta 8-Tetrahydrocannabinol (delta 8-THC) is a naturally occurring cannabinoid with a characteristic pharmacological profile of in vivo effects. Previous studies have shown that modification of the structure of delta 8-THC by inclusion of a nitrogen-containing functional group alters this profile and may alkylate the cannabinoid receptor, similar to the manner in which beta-funaltrexamine (beta-FNA) alkylates the micro-opioid receptor. Two novel analogs of delta 8-THC were synthesized: a nitrogen mustard analog with a dimethylheptyl side chain (NM-delta 8-THC) and a cyano analog with a dimethylpentyl side chain (CY-delta 8-THC). Both analogs showed high affinity for brain cannabinoid receptors and when administered acutely, produced characteristic delta 9-THC-like effects in mice, including locomotor suppression, hypothermia, antinociception and catalepsy. CY-delta 8-THC shared discriminative stimulus effects with CP 55,940; for NM-delta 8-THC, these effects also occurred, but were delayed. Although both compounds attenuated the effects of delta 9-THC in the mouse behavioral tests, evaluation of potential antagonist effects of these compounds was complicated by the fact that two injections of delta 9-THC produced similar results, suggesting that acute tolerance or desensitization might account for the observations. NM-delta 8-THC, but not CY-delta 8-THC, attenuated the discriminative stimulus effects of CP 55,940 in rats several days following injection. Hence, addition of a nitrogen-containing functional group to a traditional cannabinoid structure does not eliminate agonist effects and may produce delayed attenuation of cannabinoid-induced pharmacological effects.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 1
Cites 6
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- Delta 9-tetrahydrocannabinol discrimination in rats as a model for cannabis intoxication. Neuroscience and biobehavioral reviews 1992
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