Marijuana Ingredient May Stall Decline from Alzheimer's

March 4, 2005

Science Daily/Society for Neuroscience

New research shows that a synthetic analogue of the active component of marijuana may reduce the inflammation and prevent the mental decline associated with Alzheimer's disease.

"This research is not only a major step in our understanding [of] how the brain reacts to Alzheimer's disease, but may also help open a route to novel anti-Alzheimer's drugs," says Raphael Mechoulam, professor emeritus of medicinal chemistry at Hebrew University in Jerusalem and discoverer of marijuana's active component.

To show the preventive effects of cannabinoids on Alzheimer's disease, researchers at the Cajal Institute and Complutense University in Madrid, led by Maria de Ceballos, conducted studies using human brain tissue, as well as experiments with rats. The study appears in the February 23, 2005, issue of The Journal of Neuroscience.

The team first compared the brain tissue of patients who died from Alzheimer's disease with that of healthy people who had died at a similar age. They looked closely at cannabinoid receptors CB1 and CB2– proteins to which cannabinoids bind, allowing their effects to be felt – and at microglia, which activate the brain's immune response. Micro- glia collect near plaques and, when active, cause inflammation. The researchers found a dramatically reduced functioning of cannabinoid receptors in diseased brain tissue, meaning that patients had lost the capacity to experience cannabinoids' protective effects.

In addition, the researchers showed that cannabinoids prevented cognitive decline through rat experiments. They injected either amyloid (which leads to cognitive decline) that had been allowed to aggregate or control proteins into the brains of rats for one week. Other rats were injected with a cannabinoid and either amyloid or a control protein.

After two months, the researchers trained the rats over five days to find a platform hidden underwater. Rats treated with the control protein – with or without cannabinoids – and those treated with the amyloid protein and cannabinoid were able to find the platform. Rats treated with amyloid protein alone did not learn how to find the platform.

The researchers found that the presence of amyloid protein in the rats' brains activated immune cells. Rats that received the control protein alone or cannabinoid and a control protein did not show activation of microglia. Using cell cultures, the investigators confirmed that cannabinoids counteracted the activation of microglia and thus reduced inflammation.

"These findings that cannabinoids work both to prevent inflammation and to protect the brain may set the stage for their use as a therapeutic approach for [Alzheimer's disease]," de Ceballos says. The scientists will now focus their efforts on targeting one of the two main cannabinoid receptors that is not involved in producing the psychotropic effects, or high, from marijuana.

https://www.sciencedaily.com/releases/2005/02/050224111638.htm

New insights into the neural risks and benefits of marijuana use

Compounds in cannabis can impair or improve memory depending on age, disease

November 6, 2018

Science Daily/Society for Neuroscience

Research released today underscores both the dangers and the therapeutic promise of marijuana, revealing different effects across the lifespan. Marijuana exposure in the womb or during adolescence may disrupt learning and memory, damage communication between brain regions, and disturb levels of key neurotransmitters and metabolites in the brain. In Alzheimer's disease, however, compounds found in marijuana, such as the psychoactive compound delta-9-tetrahydrocannabinol (THC), may improve memory and mitigate some of the disease's symptoms.

Research released today underscores both the dangers and the therapeutic promise of marijuana, revealing different effects across the lifespan. Marijuana exposure in the womb or during adolescence may disrupt learning and memory, damage communication between brain regions, and disturb levels of key neurotransmitters and metabolites in the brain. In Alzheimer's disease, however, compounds found in marijuana, such as the psychoactive compound delta-9-tetrahydrocannabinol (THC), may improve memory and mitigate some of the disease's symptoms. The findings were presented at Neuroscience 2018, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.

Marijuana is the most commonly used illicit drug in the United States and its popularity is expected to rise as it is legalized in more places. It is also the illegal drug most commonly used by pregnant women, despite the potential for long-term harm to the fetus. Many people start using marijuana as teenagers -- a particularly vulnerable time as the brain is still developing -- when there is evidence for increased risk. At the same time, a growing number of people are turning to marijuana for the relief of symptoms of chronic diseases such as epilepsy and multiple sclerosis. These use patterns highlight the need to better understand the long-term effects of marijuana, particularly in sensitive populations such as unborn children and adolescents.

Today's new findings show that:

·     Prenatal exposure to THC in rats has lasting effects on metabolites in the brain, making the animal more vulnerable to stress later in life (Robert Schwarcz, abstract 609.12).

·     Rats exposed to synthetic compounds that are similar to THC during fetal development show impaired formation of the neural circuits involved in learning and memory as adolescents (Priyanka Das Pinky, abstract 424.17).

·     Cannabinoid use by adolescent rats boosts activity in brain pathways responsible for habit formation (José Fuentealba Evans, abstract 602.07).

·     In adolescent rats, cannabinoids may disturb the development of a protein lattice important for balancing excitatory and inhibitory activity in a brain region involved in decision-making, planning, and self-control (Eliza Jacobs-Brichford, abstract 645.09).

·     Long-term cannabinoid use alters metabolism and connectivity of brain regions involved in learning and memory in adult mice (Ana M. Sebastião, abstract 778.08).

·     Treating Alzheimer's disease mice with the psychoactive compound found in marijuana improves memory and reduces neuronal loss, suggesting a possible therapy for the human disease (Yvonne Bouter, abstract 467.14).

"Today's findings lend new understanding of the complex effects that cannabis has on the brain," said press conference moderator Michael Taffe, PhD, of Scripps Research Institute and an expert in substance abuse research. "While it may have therapeutic potential in some situations, it is important to get a better understanding of the negative aspects as well, particularly for pregnant women, teens, and chronic users."

https://www.sciencedaily.com/releases/2018/11/181106150418.htm