Cannabinoid Treatment Improves Cognition in Old Mice

In young mice, THC had the opposite effect.

By | May 8, 2017


Treatment with tetrahydrocannabinol (THC), the activate ingredient in marijuana, can restore cognition in old mice and induce molecular changes that make them more similar to young animals, scientists reported today (May 8) in Nature Medicine.

Previous studies have reported that as humans age, the brain’s endogenous cannabinoid system begins to decline. “What [the researchers] found here was that when we give THC, it improves these effects—which is, in my view, of major importance,” said Raphael Mechoulam, a professor at the Hebrew University in Jerusalem who was not involved this work. “I think [the study] is well done. I hope it will be repeated in other animals, and ultimately in humans.”

To assess the effects of THC on cognition, researchers at the University of Bonn in Germany and the Hebrew University administered a chronic dose of THC (3 milligrams per kilogram) through an implanted minipump for 28 days to mice aged two months (young), 12 months (mature), and 18 months (old).

The team conducted three standard tests for cognition (the Morris water maze test, which assesses spatial memory, an object recognition test, and a partner recognition test) and discovered that THC treatment abolished the performance deficits found in mature and old mice that did not receive the drug.

“The dose was so low that we didn’t detect any psychoactive effects, but it was high enough to restore the activity [to levels] that we normally see in younger mice,” said coauthor Andreas Zimmer, a professor at the University of Bonn. “And the effect of this was very striking, absolutely striking—a mouse that’s 18 months old shows massive signs of cognitive decline, [but] we couldn't tell the difference to young animals.”

In the young mice, however, the treatment had the opposite effect—THC actually impaired their performance.

The behavioral alterations were mirrored by gene expression changes in the hippocampus around four weeks after the treatment cessation. “It seems that the young brain becomes old and the old brain becomes young,” coauthor Andras Bilkei-Gorzo of the Institute of Molecular Psychiatry at the University of Bonn in Germany told The Scientist. “At first sight it was totally illogical, but I realized when we gave the same drug to a young [animal], it overdrives the cannabinoid system—it’s [non-typical] hyperactivity and they have to bear the consequences. [But] in the old, the same treatment normalizes pathological low activity.”

“It’s a consistent story that makes an incremental growth over the data that’s already out there,” Gary Wenk, a professor at Ohio State University who was not involved in the study, told The Scientist. “It’s a very small addition, in my opinion . . . but that doesn’t mean it isn’t a good study, and I believe it’s done well.” In a 2008 paper, Wenk and colleagues reported that WIN-55212-2, an analog of THC, improved memory and reduced the number of activated microglia (a key mediator of neuroinflammation) in old rats.

While a number of previous studies have linked cannabinoids with anti-inflammatory effects, Bilkei-Gorzo said that his team did not find significant changes in inflammation in their experiments. Instead, they found that the effects of THC are primarily mediated by epigenetic changes. When the team blocked histone modification with anacardic acid (a histone acetyltransferase inhibitor), the effects of THC on behavior and gene expression disappeared.

“In brain aging, THC treatment definitely decreases neuroinflammation, but again I do not think this is the major effect, at least in our study,” said Bilkei-Gorzo.

According to Chuanhai Cao, a professor at the University of South Florida who was not involved in the work, one of the major limitations of this study is that the dose of THC the researchers administered was, contrary to the authors’ claims, very high. “In other publications, most people claim that low dose is around 0.2 mg or lower, at least 10-fold lower than the dose they are using.” Cao told The Scientist. A high-dose, long-term treatment with THC can alter levels of endogenous cannabinoids and surprise the immune system, he added. 

How the effects of THC will translate to humans remains an open question. “Our main goal is to see whether THC administration to older humans improves cognitive functions,” said Zimmer. “This is something we’re planning to do, and we actually have secured the resources that are necessary to do this.”

A. Bilkei-Gorzo et al., “A chronic low dose of ?9-tetrahydrocannabinol (THC) restores cognitive function in old mice,” Nature Medicine, doi:10.1038/nm.4311, 2017. 

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Avatar of: GerryS


Posts: 36

May 9, 2017

My bet is that this is due to the effects of cannabinoids on memory.  Overstimulating the memory system in youth with cannabinoids can in the worst case scenario lead to schizophrenia.  The brain "burns out" and intelligence depletes, more likely as a cumulative effect.  Perhaps we see something related to schizophrenogenisis in these younger animals.  In humans there is a loss of brain mass over time associated with schizophrenia.  In the older animals, as memory depletes, the effects of certain cannabinoids on memory formation  may supplement the diminishing memory processes.   This is very interesting and may have implications for treating dementia at least in its early stage, though there is a need for much investigation to uncover the range of both positive and negative effects and establish a therapeutic dose with minimal side effects.    
Avatar of: Cathy247


Posts: 5

May 9, 2017

I'm a psychologist who worked as a researcher 1985-1990 at Royal Park Psychiatric Hospital interviewing hundreds of first admission psychotic patients developing a multidiagnostic interview for psychosis where we rigourously examined all aspects of their development of the illness including drug taking and I never observed any link to schizophrenia in 6 years of data collection.

My boss Prof Pat McGorry claimed the link but I'm not sure where he got that data as should be noted that although most patients had used some cannabis during their lives I didn't observe any causal link for cannabis like that was clearly evident with other drugs such as speed in terms of initial consumption or increased intake amount or the drug that correlated direvctly with the onset of psychosis.

In my experience patients began consuming cannabis as a coping mechanism after they became ill not before which undermines any claims of causation.

I don't believe marijuana cases schizophrenia, at the most it may trigger psychosis in a tiny minority of cases but that is hardly even a trend.






















Avatar of: PastToTheFuture


Posts: 101

May 10, 2017

Who'da thought?

Avatar of: PastToTheFuture


Posts: 101

Replied to a comment from Cathy247 made on May 9, 2017

May 10, 2017

It is not unusual for a person to resort to marijuana after a couple days of unending hallucinations. Apparently, the effect is remarkable. Anecdotally,,, very anecdotally, the best result may be for people that do not respond to standard medications for the condition.

Avatar of: MartyC


Posts: 1

May 16, 2017

As a retired psychologist, I want to congradulate the scientists doing contemporary research showing the benefites of Cannabis.  I have had nothing but good experiences with taking Cannabis.

I have had cancer several times, always cured or surgically removed. I also take it for my chronic PTSD and find it very helpful treating various conditions that manifest. It helps me deal with the pain I have with my Cluster Headaches.

Our politicians that keep voting against science will one day regret their limited perceptions. Maybe it is because they have never tried taking it for some condition. I wached Cannabis help many of my patients in private practice where they were safe.

Avatar of: GerryS


Posts: 36

May 16, 2017

I wonder how many people developing psychosis from adolescent exposure is enough.  I wonder how many have lived with a psychotic, endured physican and psychological abuse.  From our offices we can go home to our nice quiet homes and forget the day.  Families cannot.

So, I ask agein.  How many are necessary before it becomes a danger.  I have seen whold families decimated from the fruit of cannabinoid abuse.  In my college and high school years long ago, I noticed a couple of things that have played themselves out over and over again.  1.  Adolescent cannabinoid abusers have an immensely hard time understanding opposing opinions.  2.  Cannabinoid abusers have been the most likely to engage in abusive behaviors including physical abuse psychological abuse and sexual abuse incluing but not limited to gang rape.  Cannabinoid abusers have been the most likely to ignore societal mores that respect the wellbeing of others.  And this is beside alcohol abuse although the two with the addition of nicorine use seem to go together a good bit.  Want some names?  Sorry, societal norms forbid me from releasing that information.

We cannot reproduce the environment of the 60's which brought about the surge in drug abuse (which much more started with great names like Sigmund Freud who swore that opium was completely non-addictive).  We no longer have a world covered in pesticides like DDt but by golly the ones flooding our lawns our manufacturers swear up and are not harmful whereas the day will come when their fully deliterious impact wil begin to be known.

So I ask again.  HOW MANY IS TOO MANY?  I have never seen the north pole but I know it is there.  In my 6 decades I am still finding out there are fruit I never heard about, but they still do exist.

Avatar of: Raoul Rubinstein

Raoul Rubinstein

Posts: 13

May 18, 2017

Why isn't the headline - "THC Impairs Cognition in Young Mice"?

Cannabis, the gateway drug to tobacco.

Avatar of: seer


Posts: 1

June 10, 2017

I am interested by your thoughts GerryS that cannabis stimulates memory which could explain a negative effect in youth and a positive effect in older age.  Your later comments about families decimated by cannabis, however do not seem to take into account the idea that trauma causes cannabis use rather than cannabis causing trauma.

Agreed cannabis abusers are more likely to engage in harmful behaviours, but the causal pathway has not yet been established. 

Thanks for your thoughts nevertheless.


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