Biochemistry & Pharmacology: Open Access
Open Access
ISSN: 2167-0501
+44-77-2385-9429
ISSN: 2167-0501
+44-77-2385-9429
Maria Laura Zuccoli, Allan Barnes, Lifeng Zhang, Marylin Huestis, Da-Ting Lin and Osama A Abulseoud
University of Genoa, Italy
National Institute on Drug Abuse, USA
University of Maryland, USA
Scientific Tracks Abstracts: Biochem Pharmacol (Los Angel)
Cannabis is a psychoactive substance widely used for both medicinal and recreational purposes. Cannabis-induced acute
cognitive and motoric side effects are common and remain without effective treatment. A better understanding of
the neurobiological mechanisms underlying cannabis-related effects is urgently needed to facilitate the discovery of novel
therapeutics. We recently observed elevation in ammonia plasma concentrations during and after oral, smoke or vapor
cannabis controlled administration (54mg) to 15 healthy cannabis users. Cannabis produced significant time (p<0.05) and
treatment (p<0.001) effects, with differences in plasma ammonia between placebo and edible cannabis administration at
30 (p<0.05) and 90min (p<0.05), between placebo and vaporized (p<0.05) and smoking routes (p<0.05) at 90min. Plasma
ammonia concentration positively correlated with blood -9-tetrahydrocannabinol (THC) concentrations (p<0.05). Using a
translational approach, we then examined the acute effect of THC on plasma, liver and brain ammonia concentrations and
enzyme activity in different brain regions of mice at 1, 3, 5 and 30min after a single THC injection. We found significant
reduction in striatal glutamine synthetase (GS) activity (p<0.05) and increase in striatal ammonia concentration (p<0.05) 5min
post-injection. THC plasma concentration correlated positively with striatal ammonia (p<0.001) and negatively with striatal
GS activity (p<0.05). At 30min, we found marked increase in striatal ammonia (p<0.001), associated with significant increase
in plasma ammonia (p<0.05). For the first time, we demonstrate that plasma ammonia concentration increases after controlled
cannabis administration and we provide evidence that this increase could be generated in the brain through suppression of
striatal GS activity.
Recent Publications
1. Rangroo Thrane V, Thrane A S, Wang F, Cotrina M L, Smith N A, et al. (2013) Ammonia triggers neuronal disinhibition and
seizures by impairing astrocyte potassium buffering. Nat Med. 19(12):1643ΓΆΒ?Β?8.
2. Eid T and Lee T S (2013) Reassessing the role of astrocytes in ammonia neurotoxicity.Nat Med. 19(12):1572ΓΆΒ?Β?4.
3. Bloor R N, Wang T S, Spanel P, Smith D (2008) Ammonia release from heated 'street' cannabis leaf and its potential toxic effects
on cannabis users. Addiction 103:1671ΓΆΒ?Β?1677.
4. Landfield P W, Cadwallader L B and Vinsant S (1988) Quantitative changes in hippocampal structure following long-term
exposure to delta9-tetrahydrocannabinol:possiblemediationbygluco-corticoid systems. BrainRes. 443:47ΓΆΒ?Β?62.
Maria Laura Zuccoli obtained my medical degree from the University of Genoa, Italy, and I completed the residency in Clinical Toxicology at the University of Florence, in Italy. I am currently a PhD candidate in Experimental Medicine at the University of Genoa and a Visiting Fellow at the National Institute on Drug Abuse, in Baltimore, USA. My main research topics focus on the understanding of neurobiological mechanisms involved in the effects of widely abused substances such as cannabinoids, opioids and alcohol, using in vivo two-photon endomicroscopy, optogenetic and chemogenetic behavioral assays and molecular biology techniques.
E-mail: marialaura.zuccoli@nih.gov