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Ephedrine Neurotoxicity

Ian Goddard igoddard at erols.mom
Mon May 26 00:22:43 EST 2003

>Can you site any studies showing neurotoxicity from amphetamines?

  IAN: In addition to those John cited, the following is 
  significant since it found years-long possibly permanent
  brain damage from *low-dose* amphetamine use for 6 weeks. 
  Here is the Yale press release followed by the abstract.


YALE News Release

Yale Study of Long-Term Learning Deficits Resulting From Repeated
Amphetamine Exposure Could Help Drug Abusers 

New Haven, Conn. -- Repeated exposure to low-dose amphetamines can
cause deficits in cognitive performance that last for several years
after the exposure ends, offering insight into potential harmful
effects of chronic substance abuse in humans, a Yale study has found. 

"While previous studies show that acute amphetamine injections can
impair cognition, our report is the first to demonstrate long
lasting-over two years-and possibly permanent cognitive deficits
induced by a brief period of intermittent low-dose amphetamine
exposure," said Stacy Castner, a researcher on the study. "This
research could also lead to potential treatment of deficits in former
drug abusers as well as potential drug deterrents in adolescents and
young adults." 

To mimic the "binge/crash" pattern of drug abuse in humans, Castner
gave primates twice-daily injections of chronic amphetamine (AMPH),
five days per week for six weeks. The AMPH dose ranged from 0.1 mg/kg
to 1.0 mg/kg and was increased by 0.1 mg/kg every three drug days. 

The investigation assessed changes in behavior and videotaped the
primates to record behavioral responses to each dose of AMPH. At six
months into the amphetamine exposure, the primates were tested on an
array of cognitive tasks ranging from recognition memory, visual
discrimination and spatial working memory. Primates previously exposed
to amphetamines failed to successfully perform the tasks even with
continued testing, for up to one and a half years. 

"The results show the presence of profound cognitive deficits in the
amphetamine-treated animals," said Castner, associate research
scientist in Neurobiology. "This finding could also lead to further
understanding of other diseases involving dysregulation of the brain's
dopamine neurons." (more) 

The study, which will be highlighted at the Society for Neuroscience
annual meeting in Miami, Florida from October 23-28, is consistent
with data from human research where commonly abused drugs such as
cocaine and ecstasy have been found to produce long-lasting and
possibly permanent cognitive deficits. 

"It may be the case that even a brief period of low-dose amphetamine
abuse in early adolescence or early adulthood can produce profound
cognitive deficits that may persist for a couple of years or more
after amphetamine use has ended," said Castner. 

The investigators' ongoing research includes experiments involving
neurotransmitters that will help explain the long-lasting cognitive
deficits in primates. They are also conducting experiments to reverse
the AMPH-induced cognitive deficits in the same group of primates and
they plan to investigate the biochemical and structural changes in the
primate brain that could account for the behavioral deficits. 

This study was supported by the Center for Neuroscience in Mental
Disorders from the National Institutes of Health. Patricia S.
Goldman-Rakic, professor of neurobiology at Yale was principal


Neuropsychopharmacology  2000 Jan;22(1):4-13 

Behavioral changes and [123I]IBZM equilibrium SPECT measurement of
amphetamine-induced dopamine release in rhesus monkeys exposed to
subchronic amphetamine.

Castner SA, al-Tikriti MS, Baldwin RM, Seibyl JP, Innis RB,
Goldman-Rakic PS.

Section of Neurobiology, Yale University School of Medicine, New
Haven, CT 06510, USA.

Previously we have shown that twelve weeks of repeated low-dose
d-amphetamine (AMPH) exposure in rhesus monkeys induces a long-lasting
enhancement of behavioral responses to acute low-dose challenge. The
present study was designed to investigate the behavioral and
neurochemical consequences of a six-week regimen of low-dose AMPH
exposure (0.1-1.0 mg/kg, i.m., b.i.d.) in rhesus monkeys. SPECT
imaging of AMPH's (0.4 mg/kg) ability to displace [123I]IBZM bound to
D2 dopamine receptors in the striatum of saline control and
AMPH-treated animals prior to and following chronic treatment was
accomplished using a bolus/constant infusion paradigm. Following
chronic AMPH treatment, all monkeys showed an enhanced behavioral
response to acute AMPH challenge and a significant decrease in the
percent of AMPH-induced displacement of [123I]IBZM in striatum
compared to their pretreatment scans. These findings suggest that
relatively small changes in presynaptic dopamine function may be
reflected in significant alterations in the behavioral response to
acute AMPH challenge.

PMID: 10633485 [PubMed - indexed for MEDLINE]



  "To lengthen thy life, lessen thy meals." Ben Franklin   

  Ongoing CR monkey study update: "In the monkeys...those on
  reduced feeding since the study started are dying at a rate 
  that is about half that of the monkeys receiving a full food
  ration." Associated Press: Eating less may extend human life.
  August 1, 2002 : http://www.msnbc.com/news/788746.asp?0si=-


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