Cannabinoid Science Research Group
Lab head: Jonathon Arnold
Location: Blackburn Building, University of Sydney, Camperdown
The Cannabinoid Science Research Group, headed by Dr Jonathon Arnold, conducts a diverse range of research related to cannabis and the cannabinoids.
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.
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'.
Lab members: J Arnold (head)
Role of ABC transporters in cannabis-antipsychotic interactions
Primary supervisor: Jonathon Arnold
A quarter of schizophrenia patients use cannabis and there is little research examining the beneficial or harmful effects of cannabis use on antipsychotic drug therapy. This project aims to investigate whether cannabis use might alter the effectiveness of antipsychotic treatment in schizophrenia patients. Many antipsychotic drugs are substrates for ABC transporters. These transporters are localized at the blood brain barrier where they bind substrate drugs and transport them out of the brain back into the peripheral blood supply. Our work has shown acute cannabinoid exposure inhibits the transport function of the ABC transporters P-gp and BCRP. Therefore, cannabis-using schizophrenia patients may have increased CNS retention of antipsychotic drugs that would either assist in reducing schizophrenia symptoms and/or increase the incidence of side effects. An alternate mechanism whereby cannabis might affect the brain retention of antipsychotic drugs is by altering the expression of ABC transporters. Our preliminary data suggests that longer-term cannabinoid exposure increases P-gp expression at the blood brain barrier. Thus, chronic cannabinoid exposure may reduce brain levels of antipsychotic drugs. Taken together, this project will help illuminate a novel mechanism for cannabis-antipsychotic drug interactions.
Contact: Email Jonathon Arnold