Health - Marijuana and alcohol taken together induced widespread neuron death in young rats

[Paracelsus]

http://www.sciencedaily.com/releases...0408150512.htm

ScienceDaily (Apr. 11, 2008) — Marijuana is among the most frequently used illicit drugs by women during their childbearing years and there is growing concern that marijuana abuse during pregnancy, either alone or in combination with other drugs, may have serious effects on fetal brain development. There is strong evidence that THC, the main psychoactive component of marijuana, crosses the placenta, that maternal marijuana abuse results in intrauterine growth retardation and that infants exposed to marijuana exhibit a temporary syndrome that includes lethargy and decreased muscle tone.

Fetal exposure to THC can also result in attention deficits, learning disabilities and behavioral problems. A new study using rats found that THC combined with mildly intoxicating doses of alcohol induced widespread nerve cell death in the brain.



Led by Henrik Hansen and Chrysanthy Ikonomidou, at the Neuroscience Research Center of the Humboldt University in Berlin and the Department of Pediatric Neurology, University of Technology Dresden, Germany, researchers administered THC, a synthetic form of THC, ethanol, MK-801 (an anticonvulsant) and phenobarbital by injection to rats between 1 and 14 days old. A previous study by the same group had shown that ethanol and drugs such as sedatives, anesthetics and anticonvulsants triggered widespread nerve cell death in the developing brain of immature rodents; the current study was conducted to determine if cannabinoids had the same effect.


The results showed that THC and its synthetic form did not cause neurodegeneration when administered alone but did cause cell death when given with lower than toxic amounts of ethanol. This combined effect increased according to the dose of THC that was administered and was strongest when the rats 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 ethanol's 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."


Journal article: "Cannabinoids Enhance Susceptibility of Immature Brain to Ethanol Neurotoxicity," Henrik Hansen, Birte Krutz, Marco Sifringer, Vanya Stefovska, Petra Bittigau, Fritz Pragst, Giovanni Marsicano, Beat Lutz, Chrysanthy Ikonomidou, Annals of Neurology.

[jilola]

It would be intresting to know if there was a statistically signifcant difference between cell death with ethanol+THC and ethanol alone.

It seems to me that when claiming ethanol+THC combination causes damage one should make sure the damage is not being done by one of the combined substance alone.

acknowledge that the effect of cannabinoids on the neurotoxicity of ethanol

I though they were studying the neurotoxicity of THC? Although same chemicals are involved the order is important, imho. If only from the image point of view. What's being said, like.

[Paracelsus]

It seems that I have to emphasize relevant sections:

The results showed that THC and its synthetic form did not cause neurodegeneration when administered alone but did cause cell death when given with lower than toxic amounts of ethanol.

[jilola]

Not really.
I still question the role of ethanol in the combined case.
Was the cell death in some way different so that they were able to determine the cause was not ethanol?
If so, then the conclusion stands. If not, then there is justifiable contention that the cell damage was caused by ethanol and THC had no function in the process.

The "lower than toxic" amount of ethanol is also suspect in a neonatal brain.
Was this controlled somehow to make sure the ethanol alone was unabe to cause cell damage? That was my point in my first reply.

[trptamene]

Was an ethanol only and marijuana only used for controls?

W/O them this study is ridiculous.

[Paracelsus]

They apparently didn't use an ethanol-only control group, for two possible reasons: there is lots of previous research on ethanol neurotoxicity and the amounts needed to produce certain stages of neurotoxicity, and they used an CB1 antagonist, which prevented this enhanced neurotoxicity.

From the abstract:

Neuronal degeneration became disseminated and severe when THC was combined with a mildly intoxicating ethanol dose (3gm/kg), with the effect of this drug combination resembling the massive apoptotic death observed when administering ethanol alone at much higher doses.

The results very clearly show that THC and other CB1 agonists potentiated the neurotoxic effects of ethanol, while not being neurotoxic by themselves.

EDIT: the fact that they say that THC didn't cause neurotoxicity per se suggests that they did use a THC control.

Reputation Comments on this post:

Thanks

[jilola]

The study seems the suggest that THC increases the toxicity of ethanol.
It also states THC alone doesn't cause cell death. (Which contradicts the suggestion that THC causes ireversible changes in the brain. A good outcome, I think)

The study seems to suggest that one should not drink and smoke cannabis. It also offers a possible explanation to why drinking and smoking cannabis tends to cause bad reactions.

[trptamene]

^^The study seems to suggest ppl shouldn't give marijuana and ethanol to a child...um duh..

Unless there are other reports that show the same results with a mature brain I would not be too worried about brain damage from a few joints and couple of beers.

[old hippie 56]

Guess that where the term "stoned drunk" comes from.