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Marijuana increases alcohol toxicity in young rats
Date:4/8/2008

ts were 7 days old. THC also enhanced the neurotoxic effect of phenobarbital and MK-801 (ethanol combines the mechanism of action used by these two drugs). In addition, marijuana activates CB1 receptor levels, which causes the psychomotor, memory, cognition and pain perception changes seen with this substance in adult humans and animals. In the current study, THC combined with ethanol increased these levels, and the CB1 receptor blocker Rimonabant, an anti-obesity drug that may be beneficial in treating addiction, reduced these levels. Mice that did not have functioning CB1 receptors (knockout mice) were less susceptible to the neurotoxic effects of ethanol.

Neuronal degeneration became disseminated and very severe when THC was combined with a mildly toxic ethanol dose, the authors state, adding that since this effect was completely counteracted with the CB1 receptor blocker Rimonabant, the activation of these receptors is responsible for ethanols increased toxicity. They note that experimental evidence suggests that endocannabinoid (compounds similar to cannabinoids that are naturally produced in the body) signaling may be involved in developmental processes such as cell proliferation and survival during the formation of the central nervous system, which would account for the age-dependent effect of the THC/ethanol combination seen in this study.

The authors acknowledge that the effect of cannabinoids on the neurotoxicity of ethanol on the developing brain requires further studies with longer survival periods. With the use of behavioral and stereological techniques such studies would explore whether acute changes reflect permanent neuronal loss and lead to behavioural deficits, they conclude. The results of the acute studies have interesting potential therapeutic implications including the use of CB1 receptor antagonists for preventing brain damage in fetuses and neonates exposed to ethanol, sedative and/or anticonvulsant drugs.


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Contact: Amy Molnar
amolnar@wiley.com
Wiley-Blackwell
Source:Eurekalert

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