Potential therapy to treat detrimental effects of marijuana

October 15, 2019

Science Daily/University of Maryland School of Medicine

A new study using a preclinical animal model suggests that prenatal exposure to THC, the psychoactive component of cannabis, makes the brain's dopamine neurons (an integral component of the reward system) hyperactive and increases sensitivity to the behavioral effects of THC during pre-adolescence.

As a growing number of U.S. states legalize the medicinal and recreational use of marijuana, an increasing number of American women are using cannabis before becoming pregnant and during early pregnancy often to treat morning sickness, anxiety, and lower back pain. Although emerging evidence indicates that this may have long-term consequences for their babies' brain development, how this occurs remains unclear.

A University of Maryland School of Medicine study using a preclinical animal model suggests that prenatal exposure to THC, the psychoactive component of cannabis, makes the brain's dopamine neurons (an integral component of the reward system) hyperactive and increases sensitivity to the behavioral effects of THC during pre-adolescence. This may contribute to the increased risk of psychiatric disorders like schizophrenia and other forms of psychosis later in adolescence that previous research has linked to prenatal cannabis use, according to the study published today in journal Nature Neuroscience.

The team of researchers, from UMSOM, the University of Cagliari (Italy) and the Hungarian Academy of Sciences (Hungary), found that exposure to THC in the womb increased susceptibility to THC in offspring on several behavioral tasks that mirrors the effects observed in many psychiatric diseases. These behavioral effects were caused, at least in part, by hyperactivity of dopamine neurons in a brain region called the ventral tegmental area (VTA), which regulates motivated behaviors.

More importantly, the researchers were able to correct these behavioral problems and brain abnormalities by treating experimental animals with pregnenolone, an FDA-approved drug currently under investigation in clinical trials for cannabis use disorder, schizophrenia, autism, and bipolar disorder.

"This is an exciting finding that suggests a therapeutic approach for children born to mothers who used cannabis during pregnancy," said Joseph Cheer, PhD, a Professor of Anatomy & Neurobiology and Psychiatry at the University of Maryland School of Medicine. "It also raises important questions that need to be addressed such as how does pregnenolone exert its effects and how can we improve its efficacy? Do these detrimental effects persist into adulthood, and if so, could they also be treated in a similar way?"

The researchers concluded that as physicians caution pregnant women against alcohol and cocaine intake because of their detrimental effects to the fetus, they should also, based on these new findings, advise them on the potential negative consequences of using cannabis 

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