Between 2010 and 2011, reports about the recreational drug commonly known as “bath salts” skyrocketed, and its use has been connected with a range of serious consequences including heart attack, liver failure, prolonged psychosis, suicide, violence, and even cannibalism. The drug, which is distinct from actual bath salts and sometimes goes by other names such as “plant food,” contains synthetic cathinones, which have effects that resemble those of amphetamines and cocaine. (Natural cathinone is derived from the plant Khat, which some cultures, particularly in the Horn of Africa and the Arabian Peninsula, have used socially for its euphoric effects when chewed.)
Synthetic cathinones are not well understood, but a few studies published in the journal Neuropsychopharmacology this year provided some preliminary findings. The most common synthetic cathinone found in the blood and urine of patients admitted to emergency rooms in the US after taking bath salts is 3,4-methylenedioxypyrovalerone, or MDPV.
In a study of rats by Baumann et al., MDPV was found to have a strong blocking effect on uptake of the neurotransmitters dopamine and norepinephrine, while having only weak effects on uptake of serotonin. MDPV’s ability to inhibit the clearance of dopamine from cells is similar to cocaine’s actions, but MDPV is much more potent and effective at this. MDPV was also 10 times more potent than cocaine at producing physical symptoms in the rats, such as motor activation, tachycardia (irregular heart beat), and hypertension (high blood pressure).
Another study of rats by Fantegrossi et al. found that rats that received MDPV experienced motor stimulation that was potentiated by being in a warm environment. When the rats received relatively high doses in this environment, they engaged in profound stereotypy (repetitive movement) and self-injurious behavior such as skin-picking or chest-biting. This study also found similarities in the internal effects of MDPV and MDMA (ecstasy) and methamphetamine.
MDMA, better known as the drug ecstasy, has been found to reduce serotonin axons in animals. A small study by Di Iorio et al. published in the Archives of General Psychiatry in 2012 suggests that the drug also has detrimental effects on serotonin signaling in humans.
The researchers used positron emission tomography (PET) scans to identify serotonin receptors in the brains of 10 women who had never used ecstasy and 14 who had used the drug at least five times before and then abstained for at least 90 days. The team found significantly greater cortical serotonin2A receptor nondisplaceable binding potential (serotonin2ABPND, an indicator of serotonin receptors) in abstaining MDMA users than in those women who had never used the drug.
The increase in serotonin receptors observed in these ecstasy users could be a sign of chronic serotonin neurotoxicity. Loss of serotonin nerve terminals decreases serotonin levels and secondarily results in the production of more serotonin receptors. Thus, one explanation for the receptor increase is that it is prompted by the decrease in serotonin transmission that MDMA is known to cause.
The higher levels of serotonin2ABPND were found in several regions of the MDMA users’ brains: occipital-parietal, temporal, occipito-temporal-parietal, frontal, and frontoparietal. Lifetime use of the drug was associated with serotonin2ABPND in the frontoparietal, occipitotemporal, frontolimbic, and frontal regions. There were no regions in which the MDMA users had lower levels of receptors than women in the control group. The duration of the ecstasy users’ abstinence from using the drug had no effect on levels of serotonin2ABPND observed, suggesting that the effects might be long-lasting, if not permanent.
Editor’s Note: Given serotonin’s importance in brain function and the drug’s popularity for recreational use, this finding has implications both for ecstasy users and for research on serotonin signaling. Ecstasy is supposed to be a “love drug,” but people should show their serotonin nerve terminals some love and look after them by avoiding the drug.
German researchers have found that MDMA (ecstasy) users who took more than 10 pills in a one-year period showed deficits in visual memory. Wagner et al. published the study in the journal Addiction in 2012.
In tests where participants were trained to associate certain words with certain images and then recall one in response to the other, those who had taken ecstasy at least ten times the previous year showed deterioration in both their immediate and delayed recall skills.
Given the role of the hippocampus in relational memory, the researchers suspect that there is a relationship between ecstasy use and hippocampal dysfunction.
Editor’s Note: This is the most definitive study on this subject so far because it observed new users before and after they had used ecstasy for at least 10 times in one year (unlike many retrospective studies that observed participants only after they had been using the drug for some time, so it was impossible to know if they had pre-existing memory problems).
Other data in animals and humans suggest that ecstasy burns out the terminals of serotonergic neurons and thus causes brain damage. It now appears this damage to the brain and memory can occur even during short-term or casual ecstasy use.
Lifetime Heart Disease Risk Increases Dramatically When One or More Risk Factors Are Present in Middle Age
A meta-analysis of 18 studies that was published by Donald Lloyd-Jones in the New England Journal of Medicine in 2012 shows that increasing cardiovascular risk factors during middle age can dramatically increase a person’s risk of experiencing fatal cardiovascular disease, fatal coronary heart disease, nonfatal heart attack, or stroke later in life.
Data were analyzed from 257,384 patients, who included black and white men and women spanning a 50-year range of birth cohorts. The studies examined cardiovascular risk factors such as smoking, cholesterol levels, diabetes, and blood pressure at ages 45, 55, 65, and 75.
Having even one risk factor at age 55 dramatically increased the lifetime risk of cardiovascular disease compared to having no risk factors, and having more risk factors during middle age increased risk even further. Among people with no risk factors at age 55 (meaning cholesterol under 180mg/dL, blood pressure under 120 mm Hg systolic and 80 mm HG diastolic, nonsmoking and nondiabetic), men had 4.7% risk of death from cardiovascular disease by age 80 (compared to 29.6% for those with 2 or more risk factors). Women had a 6.4% risk of death from cardiovascular disease by age 80 (compared to 20.5% among those with 2 or more risk factors).
Lifetime risk of death from cardiovascular disease and coronary heart disease and risk of nonfatal heart attack were about twice as high in men, while risk of stroke was similar for men and women.
Across race, trends were similar, but this finding can be misleading. While African-Americans have more cardiovascular risk factors than whites, they are also more likely to die at younger ages from other causes before developing serious cardiovascular illnesses. Large studies with Latino and Asian American participants were begun too recently to provide robust data about long-term risk, but this research is expected to become available soon.
Editor’s Note: Watch your risk factors for heart disease, including high blood pressure, cholesterol, weight, and blood sugar. The more risk factors one has, the greater the increased risk of fatal cardiovascular illness.
Depression is also a risk factor for coronary artery disease, and should be treated just as aggressively and persistently as the other risk factors. Exercise is one element of a healthy lifestyle that can positively affect all of these risk factors. Implementing a healthy diet and exercise regimen by middle age will have long-term positive effects in reducing risks in older ages.
Physical activity and light to moderate drinking (as is often associated with the Mediterranean diet) are recommended as ways to reduce risk for heart disease and type 2 diabetes. New research shows that among healthy people, symptoms of depression can counteract the anti-inflammatory benefits of both exercise and light to moderate alcohol consumption.
C-reactive protein (CRP) is a cardiometabolic risk marker. High measures of CRP are a sign of inflammation. Leisure-time physical activity and light to moderate alcohol intake (defined as about half a drink per day for women and one drink per day for men) are associated with lower levels of CRP. Depression is associated with higher levels.
A study by Edward C. Suarez et al. published recently in the journal Brain, Behavior, and Immunity examined 222 nonsmoking men and women aged 18-65 years. These participants were physically healthy and had no history or diagnosis of psychiatric conditions. Participants recorded the amount of alcohol they consumed and the amount of physical activity in which they participated. CRP levels in their fasting blood samples were measured, and they also completed an inventory of depressive symptoms.
Those people who were physically active had lower levels of CRP, but the 4.5% of participants with depressive symptoms did not see any anti-inflammatory benefits from physical activity. Similarly, light to moderate drinking was associated with lower levels of CRP only in men who were not depressed.
Depression did not seem to affect other markers of physical health in this study, such as levels of triglycerides or cholesterol.
Editor’s Note: This study suggests that treating depressive symptoms should be a part of any plan to reduce cardiovascular risk. It seems that depression has effects that go beyond psychological distress and may prevent patients from reaping the benefits of their healthy behaviors. The effect of depression in preventing heart healthy changes in CRP could be one of many factors mediating the high levels of cardiovascular risk in depression. People with depression are twice as likely to have a heart attack than those without depression.
Research has connected cardiovascular fitness with depression risk and treatment. A Swedish study published last year in the British Journal of Psychiatry examined records of men conscripted into the military at age 18 and compared their cardiovascular fitness at the time with hospital records from later decades. Low cardiovascular fitness at the time of conscription was associated with increased risk for serious depression.
Editor’s Note: This study provides more evidence that exercise, which increases cardiovascular fitness and decreases many of the elements of the metabolic syndrome, is good for cardiovascular and neuropsychological health, including mood stability. It is noteworthy that exercise also increases both brain-derived neurotrophic factor or BDNF (important for neural development and long-term memory) and neurogenesis (in animals), effects shared by almost all treatments with antidepressant properties. Making exercise a routine part of a regimen aimed at medical and psychiatric health is a great idea.
As childhood obesity has increased over the past several decades, the metabolic syndrome has also become more prevalent among children and adolescents. The metabolic syndrome consists of five measures related to obesity: elevations in fasting glucose levels or insulin resistance, a high proportion of LDL (“bad” cholesterol) to HDL (“good” cholesterol), elevated triglycerides, hypertension, and abdominal obesity or high waist circumference. A patient with three of these abnormalities would be diagnosed with the metabolic syndrome.
In adults, the metabolic syndrome has been associated with neurocognitive impairments. Researchers decided to look at adolescents with the metabolic syndrome to determine whether these brain effects are a result of long-term metabolic impairment or whether they can take place after short-term periods of poor metabolism as well. In a study published by Yau et al. in the journal Pediatrics last year, 49 adolescents with the metabolic syndrome were compared to 62 adolescents without the syndrome who had been matched for similar age, socioeconomic status, school grade, gender, and ethnicity.
The adolescents with the metabolic syndrome had lower scores on tests of math, spelling, attention, and mental flexibility, as well as a trend for lower overall intelligence. In brain measures such as hippocampal volume, amount of brain cerebrospinal fluid, and microstructural integrity in white matter tracts, the seriousness of the metabolic syndrome correlated with the level of abnormality on these measures.
Editor’s Note: It seems as though even short-term problems with metabolism can lead to brain impairments like lower cognitive performance and decreased integrity of brain structures. These effects are even seen before vascular disease and type 2 diabetes are manifest.
It is doubly important, in terms of both cardiovascular and neurobiological risks, to look out for one’s medical and psychiatric health. Reducing the abnormal components of the metabolic syndrome should produce benefits for both the cardiovascular system and the central nervous system.
Almost 40% of patients with bipolar illness in the US have the metabolic syndrome, so considerable effort will be required to improve this public health crisis.
A decades-long study in New Zealand suggests that people who use marijuana persistently during adolescence lose 8 IQ points by adulthood compared to their peers who never use marijuana. Quitting or reducing cannabis use after adolescence did not restore the intellectual abilities in those who used it persistently in their youth. This is the first study of its kind that controlled for differences in functioning that existed before adolescence.
Participants took part in neuropsychological testing at the age of 13, prior to any cannabis use, and then were periodically interviewed about their use of the drug (at the ages of 18, 21, 26, 32, and 38). At age 38 they underwent IQ testing again.
Although persistent cannabis users tended to have fewer years of education, the lack of education was not responsible for the difference in adult IQ.
Those participants who only began using cannabis persistently in adulthood did not see a decline in IQ, suggesting that the adolescent brain is particularly susceptible to damage from cannabis use.
Synthetic marijuana, otherwise known as spice, skank, or K2, is not only vastly more potent than the tetrahydrocannabinol (THC) in marijuana plants, but it also lacks cannabidiol (CBD), the calming, antipsychotic substance also present in the plants. This makes spice much more likely to induce major psychiatric effects.
New evidence links use of spice during pregnancy to a tragic birth defect, anencephaly, or absence of the cerebral cortex. It can also lead to the later development of attention-deficit hyperactivity disorder, learning disabilities, memory impairment, depression, and aggression.
Effects of THC on gestation may occur as early as two weeks after conception, meaning by the time a woman realizes she is pregnant, the fetus may have been harmed by exposure to the drug.
Other new finding associate use of spice with acute coronary syndrome and the kind of acute kidney injury that can lead to the organ shutting down.
Editor’s Note: It has now been found that synthetic marijuana, or spice, can lead to psychosis, delirium, acute coronary syndrome (heart attack) in young people, and now kidney dysfunction, in addition to causing birth defects if used by pregnant women. Not only is spice made up of more potent THC without the calming effects of CBD, but it is often laced with unknown contaminants, which are likely the cause of the heart and kidney damage.
Smoking regular marijuana is bad enough—it doubles the risk of psychosis and may precipitate the onset of schizophrenia. It may also cause long-lasting effects on cognitive function. Since many states are legalizing marijuana, it is important to know the risks. In any case the risks are much more serious with the synthetic product, and synthetic marijuana should be avoided at all costs.
Physical punishment of children has long been a controversial subject. A 2012 article by Afifi et al. in the journal Pediatrics suggests that having experienced harsh physical punishment during childhood is associated with mood disorders, anxiety disorders, substance abuse and dependence, and personality disorders in adulthood.
In this study harsh physical punishment included pushing, grabbing, shoving, slapping, or hitting. Participants who had experienced more severe maltreatment in childhood (including physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect, and exposure to violence between intimate partners) were excluded from the study, and the results were adjusted for sociodemographic variables and family history of dysfunction, suggesting that physical punishment was the mediator of these effects.