Monthly Archives: June 2008

Here is a fascinating new study, using the narcolepsy drug modafinil (Provigil) for gambling.  It has also been shown to be helpful for ADD, especially the low energy and motivation states.  Enjoy!

Zack M, Poulos CX. Effects of the atypical stimulant modafinil on a brief gambling episode in pathological gamblers with high vs. low impulsivity. J Psychopharmacol. 2008 Jun 26.  

 Abstract: Pathological gambling (PG) is a serious psychiatric disorder afflicting 1-3% of the general population. Experimental evidence indicates shared neurochemical substrates for PG and psychostimulant addiction. Impulsivity characterizes one key subtype of PG. Therefore, medications that ameliorate psychostimulant addiction and impulsive syndromes might also benefit impulsive PG subjects. The atypical stimulant, modafinil reduces cocaine abuse and impulsivity in patients with ADHD.

The present study sought to determine if modafinil (200 mg) would reduce the reinforcing effects of slot machine gambling in PG subjects, and if this effect was stronger in high (H-I) vs. low (L-I) impulsivity subjects (N = 20). A placebo-controlled, double-blind, counterbalanced, repeated measures design was employed. Apart from bet size, which declined uniformly in both groups under drug, modafinil had bi-directional effects in the two groups. In H-I subjects, the drug decreased desire to gamble, salience of Gambling words, disinhibition and risky decision-making. In L-I subjects, modafinil increased scores on these indices. Modafinil also differentially affected blood pressure response to the game in the two groups.

These findings for modafinil appear to fit well with a growing literature demonstrating bi-directional effects of D2 agonists as a function of trait impulsivity. Impulsivity could critically moderate medication response in PG.

The marijuana debate continues, even though we have seen damage on SPECT scans from marijuana for many years.  The article below reports on an important new study on marijuana and brain damage published in the Archives of General Psychiatry.

Medscape News June 6, 2008 — Long-term, heavy cannabis use has been linked with structural brain abnormalities, a new study shows.

Investigators at the University of Melbourne, Australia, found the hippocampus and the amygdala tend to be smaller in heavy cannabis users compared with nonusers, with average volume reductions of 12% in the hippocampus and 7.1% in the amygdala. Cannabis use was also associated with subthreshold symptoms of psychotic disorders.

Cannibis use is a controversial topic; the authors note there are many who believe cannabis is relatively harmless and should be legally available. However, the current findings suggest otherwise.

“These findings challenge the widespread perception of cannabis as having limited or no neuroanatomical sequelae. Although modest use may not lead to significant neurotoxic effects, these results suggest that heavy daily use might indeed be toxic to human brain tissue,” they write.

It is estimated that 15 million Americans use cannabis in a given month, that 3.4 million are daily users with a duration of 12 months or more, and that every year 2.1 million start using the drug.

Led by Murat Yücel, PhD, the study is published in the June issue of Archives of General Psychiatry.

Mechanism Unclear

According to the authors, this is the first human study of long-term heavy cannabis use to show marked hippocampal volume reductions. The findings, they add, are consistent with the view that cannabis use increases the risk of psychotic symptoms.

For the study, researchers performed high-resolution structural magnetic resonance imaging (MRI) on 15 men who smoked more than 5 joints daily for more than 10 years. With an average age of 39.8 years and a mean duration of regular use of 19.7 years, the subjects had no history of polydrug abuse or neurologic/mental disorder.

MRI results from these subjects were then compared with those of 16 matched controls who did not use cannabis.

Despite the large magnitude of effect, it is unclear whether volumetric reductions are due to neuronal or glial loss, a change in cell size, or a reduction in synaptic density. The investigators say more research is needed to explain the underlying mechanisms.

The study also showed hippocampal volume in cannabis users was inversely correlated with cumulative exposure to the drug in the left, but not right, hemisphere — a finding that suggests that “the left hippocampus may be particularly vulnerable to the effects of cannabis exposure and may be more closely related to the emergence of psychotic symptoms.”

According to the investigators, “further prospective, longitudinal research is required to determine the degree and mechanisms of long term cannabis-related harm and the time course of neuronal recovery after abstinence.”

Arch Gen Psychiatry. 2008;65:694-701.

Mayo Clinic specialists present at Arizona Alzheimer’s Consortium Conference on May 30, more than 750 physician scientists, researchers, caregivers, and community advocates attended the Arizona Alzheimer’s Consortium (AAC) annual conference. For 10 years running and supporting the Mayo Clinic principle that two heads are better than one and five are even better, the AAC brings together Alzheimer’s disease (AD) experts from renowned organizations including: Mayo Clinic Banner Alzheimer’s Institute, Barrow Neurological Institute, Arizona State University, and Arizona Sun Health Research Institute. 

The AAC annual conference is designed as part community forum and part scientific session. The conference highlighted how researchers continue to make pioneering contributions to the scientific understanding, early detection and tracking of AD and to the discovery and evaluation of promising disease-slowing and prevention therapies. Individual variations in normal human memory and/or the predisposition to AD and provide targets for the discovery of AD-modifying, AD risk-reducing and memory-enhancing treatments.

Richard Caselli, M.D., Chair, Division of Neurology, and the AAC’s Clinical Director, served as a Q&A panelist and shared a special community-oriented presentation entitled The Diagnosis of Alzheimer’s Disease.

Among the research findings shared during the conference, Dr. Caselli and his colleagues revealed the following: Age-related memory decline is affected by APOE e4 genetic status such that e4 carriers show selectively steeper memory decline than noncarriers beginning at age 60. In addition, we have more good reason to stay in shape — physical fitness as determined by a stress test correlated with better memory in APOE e4/4 homozygotes who are a very high risk for developing AD. Results suggest there is less of a decline in cognitive functioning in hormone replacement therapy users; therefore hormone therapy may be helpful for maintaining women’s neural integrity and should be considered in future research. Brain imaging studies suggest the KIBRA gene is associated with both individual variation in episodic memory and predisposition for AD. Gray-matter differences suggest the possibility of gene-associated, longstanding differences in brain morphology that may lead to preferential vulnerability to the effects of brain aging, AD, or both and the associated cognitive decline.