Cocaine & amphetamines

Rat studies have indicated that high doses of amphetamines in adolescence produced significant declines in working memory as adults, and that amphetamines and cocaine can damage the brain’s ability to learn from new experiences. A human twin study also found long-term cocaine or amphetamine abuse affected attention and motor skills. Another human study suggests that cocaine use particularly affects prospective memory — which of course is heavily dependent on executive function.

One important mechanism for these effects involves the neurotransmitter dopamine. Methamphetamine abuse damages neurons that respond to dopamine. And a small imaging study found that people with different variants of the COMT gene (which affects dopamine responsiveness) were differently affected by amphetamine in regards to their performance on tasks involving working memory and executive functioning (this may explain why some people respond better to ADHD drugs).

Prenatal exposure to methamphetamine or cocaine has been found to produce structural abnormalities in the brain. For cocaine, the damage seems to lie mainly in regions regulating attention and memory. Mental retardation, according to one study, is dramatically (nearly five times) higher in cocaine-exposed children. Nevertheless, a review of 32 major studies of school-age children concludes that, with the exception of attention problems, the low IQ and poor academic and language achievement often found in those whose mothers used cocaine during pregnancy is more related to home environment than to the drug exposure.

Among those exposed to methamphetamine, the damage appears to be primarily to the striatum (significantly smaller) and the limbic system (significantly bigger). The striatum is involved in skill learning and habit formation, and motor coordination is likely to be affected.

A small study involving 20 people has found that those who were exposed to 1,8-cineole, one of the main chemical components of rosemary essential oil, performed better on mental arithmetic tasks. Moreover, there was a dose-dependent relationship — higher blood concentrations of the chemical were associated with greater speed and accuracy.

Participants were given two types of test: serial subtraction and rapid visual information processing. These tests took place in a cubicle smelling of rosemary. Participants sat in the cubicle for either 4, 6, 8, or 10 minutes before taking the tests (this was in order to get a range of blood concentrations). Mood was assessed both before and after, and blood was tested at the end of the session.

While blood levels of the chemical correlated with accuracy and speed on both tasks, the effects were significant only for the mental arithmetic task.

Participants didn’t know that the scent was part of the study, and those who asked about it were told it was left over from a previous study.

There was no clear evidence that the chemical improved attention, but there was a significant association with one aspect of mood, with higher levels of the scent correlating with greater contentment. Contentment was the only aspect of mood that showed such a link.

It’s suggested that this chemical compound may affect learning through its inhibiting effect on acetylcholinesterase (an important enzyme in the development of Alzheimer's disease). Most Alzheimer’s drugs are cholinesterase inhibitors.

While this is very interesting (although obviously a larger study needs to confirm the findings), what I would like to see is the effects on more prolonged mental efforts. It’s also a little baffling to find the effect being limited to only one of these tasks, given that both involve attention and working memory. I would also like to see the rosemary-infused cubicle compared to some other pleasant smell.

Interestingly, a very recent study also suggests the importance of individual differences. A rat study compared the effects of amphetamines and caffeine on cognitive effort. First of all, giving the rats the choice of easy or hard visuospatial discriminations revealed that, as with humans, individuals could be divided into those who tended to choose difficult trials (“workers”) and those who preferred easy ones (“slackers”). (Easy trials took less effort, but earned commensurately smaller reward.)

Amphetamine, it was found, made the slackers worked harder, but made the workers take it easier. Caffeine, too, made the workers slack off, but had no effect on slackers.

The extent to which this applies to humans is of course unknown, but the idea that your attitude to cognitive effort might change how stimulants affect you is an intriguing one. And of course this is a more general reminder that factors, whatever they are, have varying effects on individuals. This is why it’s so important to have a large sample size, and why, as an individual, you can’t automatically assume that something will benefit you, whatever the research says.

But in the case of rosemary oil, I can’t see any downside! Try it out; maybe it will help.

A study involving 42 students who were ecstasy/polydrug users has found that ecstasy, or the regular use of several drugs, affects users' prospective memory (remembering things you plan to do), even when tests are controlled for cannabis, tobacco or alcohol use. Cocaine use in particular was prominently associated with prospective memory impairment. Deficits were evident in both lab-based and self-reported measurements.

[164] Hadjiefthyvoulou, F., Fisk J. E., Montgomery C., & Bridges N. J.
(2010).  Everyday and prospective memory deficits in ecstasy/polydrug users.
J Psychopharmacol. 0269881109359101 - 0269881109359101.

Full text is available for a limited time at

An imaging study has revealed that children (aged 5-15) whose mothers abused methamphetamine and alcohol during pregnancy had structural abnormalities in the brain that were more severe than those seen in children whose mothers abused alcohol alone. In particular, the striatal region was significantly smaller, and within the group, size of the caudate correlated negatively with IQ. Limbic structures, in particularly the cingulate cortex and the right inferior frontal gyrus, were significantly bigger. The striatal and limbic structures are also known to be particularly affected in adult methamphetamine abusers.

When a pregnant woman uses cocaine, it can interrupt the flow of nutrients and oxygen to the baby, putting such children at risk for premature birth, low birth weight and many other problems. However a new review of 32 major studies of school-age children reveals that the consequences for the brain are less sweeping than feared. Although many of the children did have low IQ and poor academic and language achievement, this seems to be related more to the home environment. But direct effects of cocaine exposure significantly affected children in specific areas such as sustained attention and self-regulated behavior — areas which could lead to serious problems later in life.

Older news items (pre-2010) brought over from the old website



Amphetamine use in adolescence may impair adult working memory

Rats exposed to high doses of amphetamines at an age that corresponds to the later years of human adolescence showed significant declines in working memory as adults, long after the exposure. The researchers tested two types of amphetamine exposure: intermittent (a steady dose every other day) and "binge-escalation," in which increasing amounts of the drug were given over a period of four days, followed by a simulated binge – a high dose every two hours for eight hours on the fifth day. The type of exposure did not make a significant difference.

Stanis, J.J. et al. 2009. Amphetamine-induced deficits in a working memory task are more significant in drug-exposed adolescent rats than drug-exposed adults. Presented October 21 at the annual meeting of the Society for Neuroscience in Chicago.

Amphetamines and cocaine can damage the brain’s ability to learn from new experiences

A rat study suggests that amphetamines and cocaine can damage the brain’s ability to learn from new experiences. Rats were given either amphetamine, cocaine, or saline for 20 days, and then half were moved to new cages containing multiple levels with ramps, bridges, and a climbing chain; tunnels; and toys that were rearranged once a week to encourage continued exploration of the environment. After three and a half months, the rats who received saline solutions and had lived in a stimulating environment had a greater number of neuronal connections than those who remained in their usual environment. Rats given either amphetamines or cocaine, however, did not respond to the complex environment with a similar growth in neuronal connection.

[2385] Kolb, B., Gorny G., Li Y., Samaha A-N., & Robinson T. E.
(2003).  Amphetamine or cocaine limits the ability of later experience to promote structural plasticity in the neocortex and nucleus accumbens.
Proceedings of the National Academy of Sciences. 100(18), 10523 - 10528.

Amphetamine helps or hinders cognitive function depending on your genes

Everyone inherits two copies of the catecho-O-methyltransferase (COMT) gene, that codes for the enzyme that metabolizes neurotransmitters like dopamine and norepinephrine. It comes in two common versions. One version, met, contains the amino acid methionine at a point in its chemical sequence where the other version, val, contains a valine. Depending on the mix of variants inherited, a person's COMT genes can be typed met/met, val/val, or val/met. People with the val/val variant appear to have reduced prefrontal dopamine activity and less efficient prefrontal information processing, along with slightly increased risk for schizophrenia. People with val/met have more efficient prefrontal function, and people with met/met the most efficient.
In a recent imaging study, 27 volunteers (10 val/val, 11 val/met, and 6 met/met) performed a variety of cognitive tasks that involved working memory and executive functioning, after taking either amphetamine or a placebo. Since amphetamine boosts dopamine activity in the prefrontal cortex, the researchers predicted that the drug would enable val/val types to boost their low level of dopamine and perform better on cognitive tasks that depend on the prefrontal cortex. On the other hand, those with met/met should be hindered by amphetamine. The study confirmed these predictions - val/val subjects on amphetamine performed comparably to met/met types in normal conditions, while met/met subjects on amphetamine performed worse than subjects with val/val types in normal conditions.
Amphetamines and other drugs that affect prefrontal dopamine systems are used to treat Attention Deficit Hyperactivity Disorder (ADHD), and other psychiatric illnesses, and some people respond better than others to these medications. About 15-20% of individuals in populations of European ancestry have the met/met COMT gene type.

[1292] Mattay, V. S., Goldberg T. E., Fera F., Hariri A. R., Tessitore A., Egan M. F., et al.
(2003).  Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine.
Proceedings of the National Academy of Sciences of the United States of America. 100(10), 6186 - 6191.

Long-lasting changes in attention and motor skills after heavy stimulant abuse

A study of 50 pairs of twins, in which one of each pair had a history of cocaine or methamphetamine abuse, and the other had no history of drug abuse, found that the twin with a history of stimulant abuse performed significantly worse on several tests of attention and motor skills than did the one who had never used drugs, even after at least a year had passed since any drugs had been taken. Abusers did, however, outperform their twin on visual vigilance, a test measuring the ability to pay attention over time.

[1163] Toomey, R., Lyons M. J., Eisen S. A., Xian H., Chantarujikapong S., Seidman L. J., et al.
(2003).  A Twin Study of the Neuropsychological Consequences of Stimulant Abuse.
Arch Gen Psychiatry. 60(3), 303 - 310.

Methamphetamine abuse may permanently impair cognitive function

Methamphetamine abuse damages the nerve endings of human brain cells containing the chemical messenger dopamine. A recent study has found that methamphetamine-damaged brain cells may recover after prolonged abstinence from the drug. However, the extent of recovery may not be sufficient to restore full cognitive function, particularly in those who are did long-time, heavy users of the drug.

[1223] Ding, Y-S., Logan J., Volkow N. D., Chang L., Wang G-J., Fowler J. S., et al.
(2001).  Loss of Dopamine Transporters in Methamphetamine Abusers Recovers with Protracted Abstinence.
J. Neurosci.. 21(23), 9414 - 9418.

Prenatal exposure

One hit of crystal meth can cause birth defects

A mouse study has found that a single prenatal dose of methamphetamine (speed) can cause long-term neurodevelopmental problems in babies, especially reduced motor coordination.

[1003] Jeng, W., Wong A. W., Ting-A-Kee R., & Wells P. G.
(2005).  Methamphetamine-enhanced embryonic oxidative DNA damage and neurodevelopmental deficits.
Free Radical Biology & Medicine. 39(3), 317 - 326.

Cognitive development affected in babies exposed prenatally to cocaine

In the first study to use measures of both the mothers’ self report of their prenatal drug use, and infant meconium, which provided a physical measure of the amount of drug exposure, 415 cocaine-exposed infants born in Cleveland were compared to non-exposed infants on cognitive and motor development until age 2. Infants were tested at 6.5, 12 and 24 months. Mental retardation in the cocaine-exposed children at age 2 was 4.89 times higher than would be expected in the general population. The percentage of children with mild delays requiring intervention was almost double the rate of the high risk, non-cocaine group. The study also found that tobacco exposure had significant negative effects on infant development.

[390] Singer, L. T., Arendt R., Minnes S., Farkas K., Salvator A., Kirchner L. H., et al.
(2002).  Cognitive and Motor Outcomes of Cocaine-Exposed Infants.
JAMA. 287(15), 1952 - 1960.

Cocaine may permanently damage learning abilities in developing fetuses

Two recent studies investigating the effect of pre-natal exposure to cocaine in rats suggest that children exposed to cocaine while in the womb may have permanent changes to the part of the brain that helps control attention and memory, leading to learning deficits and symptoms that are very much like attention deficit hyperactivity disorder.

[1270] Morrow, B. A., Elsworth J. D., & Roth R. H.
(2002).  Male rats exposed to cocaine in utero demonstrate elevated expression of Fos in the prefrontal cortex in response to environment.
Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology. 26(3), 275 - 285.

[264] Morrow, B. A., Elsworth J. D., & Roth R. H.
(2002).  Prenatal cocaine exposure disrupts non-spatial, short-term memory in adolescent and adult male rats.
Behavioural Brain Research. 129(1-2), 217 - 223.