Research outline - Cannabinoid Science Research Group

Within: Bosch Institute, Discipline of Pharmacology

Overview of research program

Anticancer actions of cannabinoids

One of this group's primary research interests is studying the anticancer effects of plant-derived, endogenous and synthetic cannabinoid compounds. This group is investigating the antiproliferative effects of cannabinoids on a range of human cancer cell lines. In addition, with the increasing use cannabis by chemotherapy patients as a palliative care agent, it is important to know whether these drugs modulate multidrug resistance (MDR). MDR is a common reason for treatment failure in cancer patients. This group is currently investigating the effects of cannabinoids on the most characterised MDR transporter, p-glycoprotein.

The effect of cannabinoids and psychostimulants on the neuregulin knockout mouse

Human genetic studies have shown that the neuregulin gene seems to play a role in the pathogenesis of schizophrenia. This project aims to create an animal model of drug-induced psychosis by using the neuregulin knockout mouse model of schizophrenia. This group is investigating the effects of acute and chronic delta-9 tetrahydrocannabinol (THC) and methamphetamine on the neuregulin knockout mice and their respective wild-type controls (WT) using a variety of animal models of reward, anxiety and cognition, combined with c-fos immunohistochemistry to measure any changes in neural activity. This group will also be assessing whether these knockout animals show any differences in cannabinoid, dopamine and GABA receptors compared to WT.

THC re-intoxication

The NSW Analytical Laboratories has noted many cases of traumatic death where blood THC levels are much higher than would be expected. Since stress causes extensive mobilisation of fat reserves this observation could conceivably be explained by the severe stress of death causing THC release from fat. Other anecdotal cases support the view that extensive dieting or heavy exercise may lead to high levels of THC appearing in the blood of persons who have been cannabis-abstinent for a long time. Such findings could have major implications for the interpretation of the results of drug tests which are increasingly being used in the workplace, on the roads and in the schools of Australia and many other countries.

Interestingly, THC has a very high affinity for fatty tissue, so that whenever cannabis is consumed, substantial quantities of THC are lodged in fat. The human body has the capacity to store large quantities of THC and it may remain stored for many weeks, months or even years. Under normal conditions, the slow passive release of THC from fat cells into blood is unlikely to have major effects on the user: the levels are too low. However, this group has recently acquired evidence that under conditions where fat metabolism is greatly increased there is a substantial release of THC from fat stores into the blood. Furthermore, this group has demonstrated that this fat-released THC causes significant pharmacological effects in rats, now referred to as 'THC re-intoxication'.