Research shows using both marijuana and alcohol during early pregnancy may disrupt fetal development

New preclinical research reported in animal models shows that exposure to compounds found in marijuana called cannabinoids (CBs), which includes cannabidiol (CBD) and tetrahydrocannabinol (THC), during early pregnancy can cause malformations in the developing embryo.

Stained sections of fetal mouse brains. (Left) Control. (Right) Mouse exposed to alcohol and a cannabinoid on the 8th day of pregnancy. Black arrow highlights enlarged cerebral ventricle caused by the loss of the midline septal region.Dr. Scott Parnell, UNC Chapel Hilll

The research also demonstrated that co-exposure to CBs and alcohol increased the likelihood of birth defects involving the face and brain. The study, funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, was published in Scientific Reports.

“Prenatal alcohol exposure is a leading preventable cause of birth defects and neurodevelopmental abnormalities in the United States,” said NIAAA Director, George F. Koob, Ph.D. “Since marijuana and alcohol are frequently used simultaneously, the combined effects of cannabinoids and alcohol are worrisome as well as the dangers of either substance alone.” 

The detrimental effects of prenatal alcohol exposure on human development are well known and include an array of lifelong physical, cognitive, and behavioral problems collectively called fetal alcohol spectrum disorders (FASD). Alcohol can disrupt fetal development at any stage during pregnancy, even the earliest stages before a woman knows she is pregnant. The effects of marijuana exposure during pregnancy and the combined effect of alcohol and marijuana are less known. 

In the study, scientists led by Scott Parnell, Ph.D., at the Bowles Center for Alcohol Studies at the University of North Carolina in Chapel Hill, administered a variety of CBs alone and in combination with alcohol in varying amounts to mice on day eight of pregnancy, which is similar to the third and fourth weeks of pregnancy in humans. The CBD amounts administered were within what is considered a therapeutic range for several medical conditions in humans. The THC concentration administered was similar to levels reached by a person smoking marijuana.

The researchers found that one-time exposure to CBD and THC caused eye, brain, and facial malformations similar to those caused by prenatal alcohol exposure alone. The researchers also found that when mice were given both CBs and alcohol, the likelihood of these birth defects more than doubled. They confirmed this finding in a zebrafish model.

Further investigation by Parnell’s team revealed clues about the mechanisms by which alcohol and CBs interact at the cellular level. They found that alcohol and CBs converge on the Sonic Hedgehog pathway to inhibit signaling between molecules in cells that control growth and development in the embryo. The Sonic Hedgehog pathway plays a key role in the development of animals and humans.

“Our finding that simultaneous exposure to alcohol and CBs induces the highest rate of birth defects, even at low doses of these substances emphasizes the need for more research to better understand the effects of alcohol and CBs on the developing embryo,” said Parnell.

This news release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

Adopting a healthy lifestyle helps reduce the risk of dementia

People can reduce their risk of dementia by getting regular exercise, not smoking, avoiding harmful use of alcohol, controlling their weight, eating a healthy diet, and maintaining healthy blood pressure, cholesterol and blood sugar levels, according to new guidelines issued by the World Health Organization (WHO) today.

Exercise help helps reduce the risk of dementia. Photo credit: Harvard Health

“In the next 30 years, the number of people with dementia is expected to triple,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus. “We need to do everything we can to reduce our risk of dementia. The scientific evidence gathered for these Guidelines confirm what we have suspected for some time, that what is good for our heart, is also good for our brain.”

The Guidelines provide the knowledge base for health-care providers to advise patients on what they can do to help prevent cognitive decline and dementia. They will also be useful for governments, policy-makers and planning authorities to guide them in developing policy and designing programmes that encourage healthy lifestyles.

The reduction of risk factors for dementia is one of several areas of action included in WHO’s Global action plan for the public health response to dementia. Other areas include: strengthening information systems for dementia; diagnosis, treatment and care; supporting carers of people with dementia; and research and innovation.

WHO’s Global Dementia Observatory, launched in December 2017, is a compilation of information about country activities and resources for dementia, such as national plans, dementia-friendly initiatives, awareness campaigns and facilities for care. Data from 21 countries, including Bangladesh, Chile, France, Japan, Jordan and Togo, have already been included, with a total of 80 countries now engaged in providing data.

Creating national policies and plans for dementia are among WHO’s key recommendations for countries in their efforts to manage this growing health challenge. During 2018, WHO provided support to countries such as Bosnia and Herzegovina, Croatia, Qatar, Slovenia and Sri Lanka to help them develop a comprehensive, multi-sectoral public health response to dementia.

An essential element of every national dementia plan is support for carers of people with dementia, said Dr Dévora Kestel, Director of the Department of Mental Health and Substance Abuse at WHO. “Dementia carers are very often family members who need to make considerable adjustments to their family and professional lives to care for their loved ones. This is why WHO created iSupport. iSupport is an online training programme providing carers of people with dementia with advice on overall management of care, dealing with behaviour changes and how to look after their own health.”

iSupport  is currently being used in eight countries, with more expected to follow.

Dementia: a rapidly growing public health problem

Dementia is an illness characterized by a deterioration in cognitive function beyond what might be expected from normal ageing. It affects memory, thinking, orientation, comprehension, calculation, learning capacity, language and judgement. Dementia results from a variety of diseases and injuries that affect the brain, such as Alzheimer disease or stroke.

Dementia is a rapidly growing public health problem affecting around 50 million people globally. There are nearly 10 million new cases every year. Dementia is a major cause of disability and dependency among older people. Additionally, the disease inflicts a heavy economic burden on societies as a whole, with the costs of caring for people with dementia estimated to rise to US$ 2 trillion annually by 2030.

Researchers identify key brain circuits for reward-seeking and avoidance behavior

Previously unrecognized pathways in mice have relevance for mental health and addiction research.

Researchers have identified connections between neurons in brain systems associated with reward, stress, and emotion. Conducted in mice, the new study may help untangle multiple psychiatric conditions, including alcohol use disorder, anxiety disorders, insomnia, and depression in humans.

Researchers mapped new connections in the extended amygdala related to reward-seeking and aversion. Here neurons in that pathway are labeled in fluorescent green in a cross-section of a rodent brain.Stanford University – de Lecea lab

“Understanding these intricate brain systems will be critical for developing diagnostic and therapeutic tools for a broad array of conditions,” said George F. Koob, Ph.D., director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), which contributed funding for the study. The National Institute of Mental Health (NIMH) also provided major support for the research.  NIAAA and NIMH are parts of the National Institutes of Health.

A report of the study, by first author Dr. William Giardino and colleagues at Stanford University, appears in the August 2018 issue of Nature Neuroscience.

Responding appropriately to aversive or rewarding stimuli is essential for survival. This requires fine-tuned regulation of brain systems that enable rapid responses to changes in the environment, such as those involved in sleep, wakefulness, stress, and reward-seeking. These same brain systems are often dysregulated in addiction and other psychiatric conditions.

In the new study, researchers looked at the extended amygdala, a brain region involved in fear, arousal, and emotional processing and which plays a significant role in drug and alcohol addiction.  They focused on a part of this structure known as the bed nucleus of stria terminalis (BNST), which connects the extended amygdala to the hypothalamus, a brain region that regulates sleep, appetite, and body temperature.

The hypothalamus is also thought to promote both negative and positive emotional states. A better understanding of how the BNST and hypothalamus work to coordinate emotion-related behavior could shed light on the emotional processes dysregulated in addiction.

“These circuits, also implicated in binge drinking, are likely to be elements in understanding the detailed mechanisms driving stress-related alcohol- or drug-seeking and consummatory behaviors,” said first author Dr. Giardino.

To map the brain circuitry between the BNST and the hypothalamus, Dr. Giardino and his colleagues exposed mice to rewarding and aversive stimuli, and then visualized and manipulated the activity of neurons using fiber optic techniques.

The scientists identified two distinct subpopulations of neurons in the BNST that connect to separate populations of neurons in the lateral hypothalamus. These parallel circuits drove opposing emotional states: avoidance (aversion) and approach (preference). Different neurotransmitters were linked to aversion and preference within these neurocircuits – corticotropin releasing factor was involved in aversion, while cholecystokinin played a role in preference.

“The discovery of the unique and opposing influences of these specific BNST to LH circuits may be broadly relevant to the fields of neuroscience and mental health,” said senior author Luis de Lecea, Ph.D., Professor of Psychiatry and Behavioral Sciences at Stanford University.

The authors note that future studies of the BNST to LH pathways will inform the development of improved therapeutic approaches for psychiatric disorders.

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

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The National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, is the primary U.S. agency for conducting and supporting research on the causes, consequences, diagnosis, prevention, and treatment of alcohol use disorder. NIAAA also disseminates research findings to general, professional, and academic audiences.

NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases.