Baltimore, MD - Heavy, chronic use of marijuana causes increased levels of apolipoprotein C3 (apoC3), which in turn results in a major increase in triglyceride levels, a small study shows [1]. The findings may explain some of the vascular effects of marijuana that have been observed, say Dr Subramaniam Jayanthi (National Institute on Drug Abuse, Baltimore, MD) and colleagues in their paper published online May 13, 2008 in Molecular Psychiatry.

Senior author Dr Jean Luc Cadet (National Institute on Drug Abuse) told heartwire: "A lot of people in cardiology have probably not been following the literature on marijuana, as most of it comes from the perspective of the neurologist or neuropsychiatrist. But in researching this topic, we came across a lot of papers suggesting that marijuana has acute cardiovascular effects, and we ourselves published a paper in 2005 showing that heavy marijuana users had increased resistance to brachial flow."

Cadet says the new finding of a substantial increase in apolipoprotein C3 in heavy marijuana users "requires confirmation," but it should prompt doctors to ask patients about marijuana use. Marijuana is the most commonly abused drug in the US, and "most cardiologists are not thinking of marijuana as a drug with major medical toxicity," he notes, "but there is evidence of cardiovascular side effects that might be related to the elevation in apolipoprotein C3 that we saw."

Most cardiologists are not thinking of marijuana as a drug with major medical toxicity.

In their paper, Jayanthi et al explain that the physiologic effects of marijuana are mediated via the active ingredient, tetrahydrocannabinol (THC), binding to cannabinoid receptors that are found in the brain and in the periphery, including in the heart, liver, kidney, spleen, small intestine, testes, and ovaries. Research has already shown that marijuana abuse causes increased resistance to blood flow and may increase the risk of certain cardiovascular disorders, they note.

Hence, they decided to test the possibility that marijuana use might be associated with changes in serum protein levels using a new proteomic approach. They examined 18 heavy marijuana users and 24 controls and found that the marijuana users had significant increases in three protein peaks, which were identified as three isoforms of a major lipoprotein, apoC3. The latter is a cardiovascular risk factor, and the present study "has now identified apolipoprotein C3 as a possible agent in the complex network of marijuana-induced effects in humans," they note.

They also found significant correlations between apoC3 and triglyceride levels. The mean triglyceride level in the 18 marijuana users was 122.0 mg/dL, compared with 91.17 mg/dL in the 24 controls. This is consistent with a previous paper—albeit 20 years old—that reported significant increases in HDL-triglyceride concentrations in marijuana users compared with controls, they note.

"The observed increases in apolipoprotein C3 in the marijuana users hint of the possibility that chronic marijuana abuse could lead to impairments of cellular energetics and mitochondrial function, which are critical events associated with myocardial infarction, stroke, and ischemic/reperfusion damage," they say.

In conclusion, Cadet stressed to heartwire that this is a small study, "and we'd like to see a larger group of people evaluated to see if this really holds. But in the meantime, doctors should ask patients about a history of drug abuse, and if they have been smoking marijuana, it may be worth checking triglyceride levels."