Cannabis and the endocannabinoid system: an interview with Dr Leonora Long


Please could you describe what effects cannabis has on the body?

Cannabis has both physical and behavioural effects. People using cannabis can experience feelings of euphoria (well-being), hunger, sleepiness, problems with motor coordination, and sometimes feelings of anxiety and paranoia.

How does cannabis act on the brain?

Chemicals in the cannabis plant attach to proteins in the brain called CB1 receptors. CB1 receptors are located on cells in the brain called neurons. Normal brain functions, like memory and decision-making, rely on these neurons communicating with each other, and CB1 receptors help to ‘fine tune’ this communication. So if cannabis compounds attach to these CB1 receptors, they can disrupt the normal regulation of communication in the brain.

Could you please give a brief introduction to the endocannabinoid system?

The body makes its own cannabis-like chemicals, called endocannabinoids. These endocannabinoids act like messengers between the cells of the body. In the brain, endocannabinoids attach to CB1 receptors located on neurons to modify the way that the neurons communicate with each other.

Specialised proteins called enzymes help to make the endocannabinoid messengers when they are needed, and other enzymes break down the endocannabinoids when they are no longer required. Together, the endocannabinoid messengers, the receptors they attach to, and these specialised enzymes make up the endocannabinoid system.

How does the endocannabinoid system change during adolescence?

We have looked at how the endocannabinoid system develops in the brain across the human lifespan from newborns to adults. We have found that some of the most dramatic change happens in adolescence. We see that the brain’s capacity to make CB1 receptors is declining, compared with very early life when this capacity is very high. On the other hand, one of the enzymes that helps to make the endocannabinoid messengers is higher at adolescence than it is in toddlerhood or adulthood, suggesting that there is still a great need for these messengers to help with communication in the brain.

Can using cannabis during adolescence disrupt these changes?

During adolescence, the brain is trying to ‘settle’ itself, to achieve the right balance in communication between neurons. This is crucial for the transition from adolescent to adult behaviour. For example, the risky behaviour common in teenagers is less prominent by the time a person is in their mid-twenties. Since the endocannabinoid system is a part of the process by which the brain balances its communication, and since it seems to be working very hard to sculpt these connections during adolescence, exposure to cannabis at this time could have a higher impact than in adulthood, when the brain's connections are more stable.

Please could you explain how your research showed that using cannabis during adolescence can have consequences for the development of healthy brains in adults?

Well, we haven’t investigated the impact of cannabis use on the molecules we studied in the brain samples, since the samples came from people who had not been exposed to cannabis. However, knowing what is happening in these healthy brain samples is very helpful, since it gives us a comparison for future experiments looking at how the endocannabinoid system is changed in the brains of people with illnesses like schizophrenia, for example.

What impact do you think your research will have?

We know that people who use cannabis, particularly earlier in life, are at greater risk of developing illnesses like schizophrenia, and of an earlier onset of these illnesses. We also see that in the brains of people with schizophrenia, there are changes in the molecules of the endocannabinoid system. So, if we can understand what goes wrong in the normal developmental patterns that we have identified, we can look towards developing treatment strategies that prevent or modify the changes in schizophrenia, which may help to alleviate the symptoms of the illness.

How does the damage that cannabis causes compare to the damage caused by alcohol and other drugs?

Alcohol, cannabis and other drugs all exert their effects in different ways, since they attach to different molecules in the body. The extent of detrimental effects of any drug depends on the individual and how long and how much drug use has occurred. We still don’t know the full mechanisms by which cannabis causes its detrimental effects, but studies so far show that negative effects of cannabis exposure, such as problems with social interaction and memory, may be due to changes in certain proteins in the brain.

Where can readers find more information?

My latest paper in BMC Neuroscience:

Our research group page at

The NeuRA blog:

About Dr Leonora Long

Leonora Long BIG IMAGELeonora is a research officer with the Shannon Weickert group at Neuroscience Research Australia. Her work combines developmental neurobiology and endocannabinoid pharmacology to determine the role of genetic and environmental factors in causing schizophrenia. Leonora began professional life as a pharmacist, practicing in hospital and community pharmacy and specialising in psychiatry and addiction pharmacotherapy. Building on these interests, her PhD (Monash University 2006) investigated the effects of cannabinoid ligands on sensorimotor gating and its molecular correlates in rodents. Her postdoctoral work focused on the neurobehavioural effects of THC and cannabidiol, two cannabis compounds, in a genetic mouse model of schizophrenia symptoms. She is currently investigating how the endocannabinoid system develops in the normal human brain, and how mutation in a schizophrenia risk gene, neuregulin 1, impacts on development of genes, proteins and behaviours associated with schizophrenia.

April Cashin-Garbutt

Written by

April Cashin-Garbutt

April graduated with a first-class honours degree in Natural Sciences from Pembroke College, University of Cambridge. During her time as Editor-in-Chief, News-Medical (2012-2017), she kickstarted the content production process and helped to grow the website readership to over 60 million visitors per year. Through interviewing global thought leaders in medicine and life sciences, including Nobel laureates, April developed a passion for neuroscience and now works at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour, located within UCL.


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  1. savatage savatage United States says:

    Since you "know that people who use cannabis, particularly earlier in life, are at greater risk of developing illnesses like schizophrenia" could you elighten us as to why there were no increase of said ilnesses when cannabis became popular? Schizophrenia percentages have remained flat before and during our massive increase in cannabis consumption. I've consumed cannabis since before my teens and am fine. My brothers have both partaken of this blessed herb for OVER 50 YEARS EACH. Both are happy, healthy and have their own successful businesses and families. You "just know" it causes schizophrenia and other diseases? No you don't. You must have stock in the pharmaceutical or alcohol industry to regurgitate this Reefer Madness baloney. The 50s called. They want their attitude towards cannabis (and their hairstyle and glasses) back, grandma.

    • Kerbox Kerbox Australia says:

      They do not want to answer that or consider other variables on this subject, they just want to solely focus on endlessly suggesting there is a link to cannabis and schizophrenia because it is the only line politicians are left with to try to justify continued prohibition.

      Recently schizophrenia has even been linked to infection in early childhood, it is also a brain degenerative disease with genetic predisposition but apparently those things are not important neither. It is clearly a very complex condition, I also have no doubt cannabis use can be linked to an onset of it but clearly it can not cause it outright, anyone who claims so should have no place trying to put out anything resembling real science.

      Regardless all these excuses for continued prohibition have little impact on the massively failed war on drugs and if we want to understand these issues better and treat those who may be at risk of an early onset or some developing psychosis it needs to be legalised, studied properly and the public educated on it properly. Ironically cannabinoids have also been found to have anti-psychotic effects and is speculated as to why people with schizophrenia actually use the drug, while clearly THC is the culprit in making symptoms worse.

  2. GreenPete GreenPete United Kingdom says:

    Were these questions and answers edited by the blog writers of the daily mail by any chance?
    Not one of the hundreds of positive effects that THC, CBD or CBN has on the endocannabinoidal system and the brain, and the body even have a mention here.
    Sativex, Dronabinol/Marinol, Nabilone/Cesamet, Dexanabinol, CT-3 (ajulemic acid), PRS-211,375, HU 308 & HU 331, Rimonabant/Acomplia, Taranabant/MK-0364, O-3246 and AM 281.
    (all developed directly from Cannabinoids or their effects on the CB1 & CB2 receptors).

  3. nota realperson nota realperson United Kingdom says:

    A trip to any online seedbank would show you that there is not just one type of cannabis. A few moments' research will show you there are varieties with high and low thc content and some strains developed for their CBD content. A company working in Israel has reputedly developed a strain producing <1% THC9 and over 20% CBD. As CBD is often described as an anti-psychotic ()indeed has been prescribed to treat psychosis in some cases did your research include investigating the effects of that compound?  

    Can research not based on samples from people who have had the exposure you describe does it carry more or less weight than research that uses samples from people that have?

  4. Jennifer Donley Sellers Jennifer Donley Sellers United States says:

    Although the effect on teen brains may be accurate, this entire series of articles will turn people away from the amazing treatment marijuana can be for a myriad of diseases.  You need to do a series of articles on the work of Rick Simpson and the many cures he has witnesses.  Even Sanjay Gupta is trying to spread the message.  Teenagers are always going to try something, liquor, prescription meds, whatever they can get if they are so inclined.  This is not a good message for very ill people who need more than modern medicine can provide.

  5. Jay Kaneshiro Jay Kaneshiro United States says:

    HAHAHAHA WOW, really? What a bunch of shit!! There is living proof that thousands can back up, that cannabis does the opposite effect of this. Paranoia does happen but that is only due to a to much thc and not enough CBD.. Which can easily be given the right dose to any person. I swear these people are doing all they can to try and keep us away from being sustainable on our own.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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