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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.

Paris, France: The administration of oral THC in rats suppresses sensitivity to opiate dependence, according to preclinical findings published in the June 24 issue of the journal Neuropsychopharmacology.

An international team of researchers from France and Canada assessed the impact oral THC (dronabinol) exposure in maternally deprived rats.(Rats that are deprived of their mothers immediately after birth are far more vulnerable to opiate dependence than non-deprived subjects.)

“Dronabinol treatment on maternally deprived rats normalized morphine consumption and suppressed sensitivity to morphine conditioning,” researchers reported. “These findings point to the self-medication use of cannabis in subgroups of individuals subjected to adverse postnatal environment(s).”

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).

Daugé’s team 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.

The clinical data  published this month in the July/August issue of the American Journal on Addictions reported that drug treatment subjects who used cannabis intermittently were more likely to adhere to treatment for opioid dependence

Commenting on the studies, NORML Deputy Director Paul Armentano said, “These findings undermine the notion that cannabis is a so-called ‘gateway’ to hard drug use. Rather, these results indicate that in certain populations marijuana may be a useful tool for deterring the initiation or continuation of hard drug abuse.”

For more information, please contact Paul Armentano, NORML Deputy Director, at: paul@norml.org . Full text of the study, “Adolescent exposure to delta-9-THC blocks opiate dependence in maternally deprived rats,” appears in Psychopharmacology.