Sunday, July 09, 2006

Study fails to find pot is a gateway drug, declares pot a gateway drug anyway   posted by Coffee Mug @ 7/09/2006 11:23:00 PM

Don't believe everything that you breathe. You get a parking violation and a maggot on your sleeve. - Beck

This is a little egregious.

Cannabis use is a hypothesized gateway to subsequent abuse of other drugs such as heroin. We currently assessed whether Delta-9-tetrahydrocannabinol (THC) exposure during adolescence modulates opiate reinforcement and opioid neural systems in adulthood. Long-Evan male rats received THC (1.5 mg/kg intraperitoneally (i.p.)) or vehicle every third day during postnatal days (PNDs) 28-49. Heroin self-administration behavior (fixed ratio-1; 3-h sessions) was studied from young adulthood (PND 57) into full adults (PND 102). THC-pretreated rats showed an upward shift throughout the heroin self-administration acquisition (30 mug/kg/infusion) phase, whereas control animals maintained the same pattern once stable intake was obtained. Heightened opiate sensitivity in THC animals was also evidenced by higher heroin consumption during the maintenance phase (30 and 60 mug/kg/infusion) and greater responding for moderate-low heroin doses (dose-response curve: 7.5, 15, 30, 60, and 100 mug/kg/injection). Specific disturbance of the endogenous opioid system was also apparent in the brain of adults with adolescent THC exposure. Striatal preproenkephalin mRNA expression was exclusively increased in the nucleus accumbens (NAc) shell; the relative elevation of preproenkephalin mRNA in the THC rats was maintained even after heroin self-administration. Moreover, mu opioid receptor (muOR) GTP-coupling was potentiated in mesolimbic and nigrostriatal brainstem regions in THC-pretreated animals. muOR function in the NAc shell was specifically correlated to heroin intake. The current findings support the gateway hypothesis demonstrating that adolescence cannabis exposure has an enduring impact on hedonic processing resulting in enhanced opiate intake, possibly as a consequence of alterations in limbic opioid neuronal populations.

Pete and friends over at DrugWarRant hit this pretty hard. They seem a little more negative about animal research than I'd like, but give it a look.

Here are some major criticisms:
  • The gateway hypothesis as presented to the public is that marijuana use will increase the likelihood of use and abuse of other drugs.
  • The study reports the opposite of this prediction:
    The periodic exposure to low-dose THC during adolescence did not appear to predispose animals to an increased sensitivity to initiate heroin self-administration.
  • If anything, THC exposure seems to have made it easier to go off of the stuff when they unhooked the levers from the heroin administration:
    Our experiment showed that in the absence of heroin and associated cues, both THC and vehicle-pretreated rats had similar elevated rates of responding on the active drug lever. Although the vehicle-exposed rats showed a higher percent increase in active responses than the THC rats, the behavior was not discriminative to the active lever since the control rats also had a higher increase in responding on the inactive lever.
  • Nowhere in the study did they compare THC administration in adolescents versus adults, and yet the authors emphasize adolescence. Where on earth does this quote in the Science write-up come from?
    "The important finding is the fact that adolescence is a time of increased vulnerability to drugs," says neuropharmacologist Sari Izenwasser of the University of Miami School of Medicine in Florida, who notes that such behavior may alter fundamental brain processes.
I don't have any problem believing the gateway drug idea in principle. It seems quite plausible that drugs that have similar effects (positive hedonic value) will act at the same synapses and perhaps alter the future plasticity of those synapses, but please don't try to use this study to scare your kids. You'll lose all your credibility in a few years when the 99% of their little pothead buddies never go near the heavy stuff. If you need a drug to keep your kids off of, try alcohol.