Marijuana Active Ingredient In Cannabis Eliminates Morphine Dependence

Active Ingredient In Cannabis Eliminates Morphine Dependence In Rats

ScienceDaily (July 15, 2009) — Injections of THC, the active principle of cannabis, eliminate dependence on opiates (morphine, heroin) in rats deprived of their mothers at birth. The findings could lead to therapeutic alternatives to existing substitution treatments.

In order to study psychiatric disorders, neurobiologists use animal models, especially maternal deprivation models. Depriving rats of their mothers for several hours a day after their birth leads to a lack of care and to early stress. The lack of care, which takes place during a period of intense neuronal development, is liable to cause lasting brain dysfunction.

The study was carried out by Valérie Daugé and her team at the Laboratory for Physiopathology of Diseases of the Central Nervous System (UPMC / CNRS / INSERM).

Valérie Daugé's team at the Laboratory for Physiopathology of Diseases of the Central Nervous System (UPMC / CNRS / Inserm) analyzed the effects of maternal deprivation combined with injections of tetrahydrocannabinol, or THC, the main active principle in cannabis, on behavior with regard to opiates.

Previously, Daugé and her colleagues had shown that rats deprived of their mothers at birth become hypersensitive to the rewarding effect of morphine and heroin (substances belonging to the opiate family), and rapidly become dependent. In addition, there is a correlation between such behavioral disturbances linked to dependence, and hypoactivity of the enkephalinergic system, the endogenous opioid system.

To these rats, placed under stress from birth, the researchers intermittently administered increasingly high doses of THC (5 or 10 mg/kg) during the period corresponding to their adolescence (between 35 and 48 days after birth). By measuring their consumption of morphine in adulthood, they observed that, unlike results previously obtained, the rats no longer developed typical morphine-dependent behavior. Moreover, biochemical and molecular biological data corroborate these findings. In the striatum, a region of the brain involved in drug dependence, the production of endogenous enkephalins was restored under THC, whereas it diminished in rats stressed from birth which had not received THC.

Such animal models are validated for understanding the neurobiological and behavioral effects of postnatal conditions in humans. In this context, the findings point to the development of new treatments that could relieve withdrawal effects and suppress drug dependence.

The enkephalinergic system produces endogenous enkephalins, which are neurotransmitters that bind to the same receptors as opiates and inhibit pain messages to the brain.

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Marijuana Cuts Lung Cancer Tumor Growth In Half, Study Shows

ScienceDaily (Apr. 17, 2007) — The active ingredient in marijuana cuts tumor growth in common lung cancer in half and significantly reduces the ability of the cancer to spread, say researchers at Harvard University who tested the chemical in both lab and mouse studies.

They say this is the first set of experiments to show that the compound, Delta-tetrahydrocannabinol (THC), inhibits EGF-induced growth and migration in epidermal growth factor receptor (EGFR) expressing non-small cell lung cancer cell lines. Lung cancers that over-express EGFR are usually highly aggressive and resistant to chemotherapy.

THC that targets cannabinoid receptors CB1 and CB2 is similar in function to endocannabinoids, which are cannabinoids that are naturally produced in the body and activate these receptors. The researchers suggest that THC or other designer agents that activate these receptors might be used in a targeted fashion to treat lung cancer.

"The beauty of this study is that we are showing that a substance of abuse, if used prudently, may offer a new road to therapy against lung cancer," said Anju Preet, Ph.D., a researcher in the Division of Experimental Medicine.

Acting through cannabinoid receptors CB1 and CB2, endocannabinoids (as well as THC) are thought to play a role in variety of biological functions, including pain and anxiety control, and inflammation. Although a medical derivative of THC, known as Marinol, has been approved for use as an appetite stimulant for cancer patients, and a small number of U.S. states allow use of medical marijuana to treat the same side effect, few studies have shown that THC might have anti-tumor activity, Preet says. The only clinical trial testing THC as a treatment against cancer growth was a recently completed British pilot study in human glioblastoma.

In the present study, the researchers first demonstrated that two different lung cancer cell lines as well as patient lung tumor samples express CB1 and CB2, and that non-toxic doses of THC inhibited growth and spread in the cell lines. "When the cells are pretreated with THC, they have less EGFR stimulated invasion as measured by various in-vitro assays," Preet said.

Then, for three weeks, researchers injected standard doses of THC into mice that had been implanted with human lung cancer cells, and found that tumors were reduced in size and weight by about 50 percent in treated animals compared to a control group. There was also about a 60 percent reduction in cancer lesions on the lungs in these mice as well as a significant reduction in protein markers associated with cancer progression, Preet says.

Although the researchers do not know why THC inhibits tumor growth, they say the substance could be activating molecules that arrest the cell cycle. They speculate that THC may also interfere with angiogenesis and vascularization, which promotes cancer growth.

Preet says much work is needed to clarify the pathway by which THC functions, and cautions that some animal studies have shown that THC can stimulate some cancers. "THC offers some promise, but we have a long way to go before we know what its potential is," she said.

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