Research

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Drug Discovery

Existing drugs used to treat psychiatric disorders are often rather blunt instruments that can have low efficacy and cause serious side effects. With our Drug Discovery partners in the laboratories of Professor Michael Kassiou and A/Prof Mary Collins we are involved in the development of novel medications for anxiety, depression and addiction. This goes all the way from in vitro screening through behavioural screening in rodents all the way to small scale human clinical trials. Current targets include brain oxytocin and vasopressin receptors (social anxiety, autism, addictions) TSPO receptors (panic, phobias) P2X7 receptors (depression) and the high affinity GHB binding site (insomnia).


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Oxytocin and Social Behaviour

There is major interest in oxytocin as a fundamental mediator of affiliative behaviour and wellbeing in mammals. Our laboratory became interested in it as an important mechanism through which popular party drugs such as MDMA (Ecstasy) act to increase social behaviour. More recently we have developed novel drugs (e.g. synthetic oxytocin-like compound 1 (SOC-1)) working on the oxytocin receptor that increase social behaviour in rodents. We have also been examining the efficacy of oxytocin-like compounds in treating addictions. Current projects are conducted with our colleagues Prof Michael Kassiou, A/Prof Glenn Hunt, A/Prof Adam Guastella and PhD students Callum Hicks, Michael Bowen, and Linnet Ramos.


 

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Cannabis

Cannabis is the most widely used illicit drug in the world, yet many of its effects are still quite mysterious. In conjunction with Dr Wendy Swift, Dr Kong Li, Mr Alex Wong and Dr Jonathon Arnold our lab is conducting the first ever study of the potency of street cannabis seized by police in NSW. Other clinical trials with A/Prof Nick Lintzeris, Dr Adam Winstock, Prof Jan Copeland and Dr Jennifer Johnston and Mr Alex Wong are examining novel treatments (e.g. Lithium, Oxytocin, Sativex) to help heavy cannabis users quit the drug. We are also looking at “reintoxication” effects in humans and rats: how food deprivation, exercise and stress cause THC to come out of fat stores and into the body.

Recent topics we have addressed include:

  • Examining the effects of cannabinoids on cognitive function, with a particular emphasis on cognitive flexibility.
  • Whether THC, the active component of cannabis, can be released from fat stores back into blood to cause “re-intoxication”.
  • The moderating effects of cannabidiol (CBD) on the effects of THC.
  • Optimal strategies and novel medication approaches for cannabis withdrawal.
  • Current potency of cannabis sezied by police in NSW.
  • Whether the adolescent brain is more vulnerable to adverse effects of cannabis.

 


 

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Party Drugs

Do you know your Meow-Meow from your Woof-Woof? Do you know the active ingredients of K2, Spice or TrainWreck? Young people are increasingly using novel party drugs, often bought over the internet. Often the possible hazards associated with these drugs are not well characterised. We currently have projects examining the addictive and possible toxic effects of mephedrone (Meow-Meow), and synthetic cannabinoids. This follows on from our extensive historical work on the drugs MDMA (Ecstasy) and Methamphetamine (Ice). These projects involve PhD students Craig Motbey, Linnet Ramos and Richard Kevin.

Ongoing projects include the following:

  • The possible toxicity of novel party drugs such as mephedrone (Meow)
  • Long-term effects of party drugs on brain and behaviour.
  • Mechanisms underlying the social effects of MDMA and GHB with a particular interest in the neuropeptide oxytocin.
  • The patterns of neural activation produced by party drugs, as determined by c-fos immunohistochemistry.
  • The ability of oxytocin to decrease methamphetamine craving.
  • The cognitive and behavioural effects of synthetic cannabinoids

 


 

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The Adolescent Brain

The human brain undergoes major developmental changes throughout adolescence and early adulthood and this is also peak time of substance misuse and mental health difficulties. We use animal models to examine the differential effects of alcohol, recreational drugs and prescription drugs (e.g. antidepressants, ADHD meds) on adolescent versus adult brains. We also examine how acute and chronic stress during adolescence can impact adult personality and behaviour. This work is being conducted by PhD student Emily Karanges and research assistant Michael Kendig.


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Alcohol

Alcohol related problems are estimated to cost the Australian community more than $5 billion per year. With my colleagues Michael Bowen and Michael Kendig, I have undertaken research that looks at the nature and treatment of alcohol craving. This research takes advantage of the the prodigious appetite that rats have for consuming standard off-the-shelf beers. This research has been funded by the Australian Research Council and the NHMRC. We are also involved in studies of human alcohol dependent populations in conjunction with A/Prof Adam Guastella, Dr Andrew Kemp and Dan Quintana.

Recent experiments include the following:

  • Examination of alcohol effects on the adolescent brain.
  • Assessing the extent to which beer is consumed for intoxication versus calories.
  • Identification of the possible neural substrates of alcohol craving and drugs that block alcohol craving.
  • Development of novel strategies for treating alcohol craving including the use of oxytocin.
  • Examination of chronic aclohol effects on heart rate variability.

 


 

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Olfaction and Fear

Laboratory rats exposed to the odour from the fur of a natural predator (cat) show a strong and prolonged anxiety response. This is despite the fact that they have never actually met a cat before! This powerful innate anxiety response to cat odour in rats may be analogous to certain human anxiety states such as phobias. We have used this as an animal model of innate fears in humans and explored the neural basis and pharmacology of this response. We also continue to search for the chemical component that gives rise to this effect. This work is being undertaken by Michael Kendig, Richard Kevin, Michael Bowen and Matthew May.

Ongoing projects include:

  • Whether and how cat odour-induced anxiety is decreased by anxiolytic drugs such as benzodiazepines.
  • Whether the odour-induced anxiety habituates with repeated exposure to the odour.
  • Identification of brain activation produced by cat odour.
  • Identification of the chemicals that cats secrete which cause the anxiety response in rodents.

 


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Outreach and Training

A major mission of the Psychopharmacology Laboratory is to educate the wider community about the effects of recreational drugs and prescription psychotropic drugs. Professor McGregor undertakes training workshops in the field of Psychopharmacology aimed at mental health professionals and gives frequent public lectures and invited educational talks about the work of the laboratory. We are particularly interested in educating young people about drugs and the brain.