This post summarizes The Long-term Effects of Cocaine Use on Cognitive Functioning: A Systematic Critical Review. The punchline is:
The current evidence does not support the view that chronic cocaine use is associated with broad cognitive deficits. The view that cocaine users have broad cognitive deficits is inaccurate based upon current evidence, and the perpetuation of this view may have negative implications for treatment programs and development of public policies.
This is of interest to me, because cocaine may have short-term benefits as a stimulant, and may have fewer cognitive impacts than alcohol. I am not an expert in this field, and am mostly posting in the hopes that Cunningham’s Law will hold and someone will correct my misunderstandings.
- Cocaine may lead to increases in free radicals, oxidative stress, catalase activity etc. These precursors are used synonymously with “neurotoxicity” by e.g. this paper.
- But cocaine use does not seem to lead to long-term depletion of relevant neurotransmitters. This is especially remarkable given that tests on nonhuman animals usually involve absurdly large dosages.
- Normal human usage also has several differences with experimental procedures which make human use less likely to be neurotoxic: slow ramp-up (rather than having a huge dose the first time you use it) and dosing at will (rather than having a large dose forced on you when you aren’t feeling well).
- Question: if cocaine was causing oxidative stress DNA damage (e.g. as suggested here), how likely is it that we would see a decrease in neurotransmitters large enough to be measurable in the usual study formats?
- Changes in the prefrontal cortex
- Under very large dosages, changes in the prefrontal cortex are observed in nonhuman animals: synaptic excitability, glucose metabolism, etc. These changes are accompanied by measurable differences in cognitive ability.
- Longitudinal studies in nonhuman primates showed decrease in cognitive performance after cocaine use, but differences had disappeared by three months of abstinence. After 20 months, cocaine-experienced monkeys had significantly greater metabolic activity in the cerebellum, but no difference in task performance.
- “Considered together, converging evidence suggests that the compensatory neuroplastic changes associated with chronic cocaine exposure likely create conditions where cognitive performance is normalized during acute intoxication, declines during withdrawal, and recovers gradually over the course of abstinence”
- Human studies
- These generally suffer from methodological problems. Control subjects are not matched on age, sex, education, etc. They also are generally correlational and can’t determine causation.
- Some research finds brain structure differences between cocaine using versus non-using participants. Authors usually conclude that this may explain claimed cognitive deficits in cocaine users, even if the authors did not test to see whether their participants actually had those cognitive deficits or differences could be explained by e.g. age of participants.
- Cocaine abusers may have different concentrations of white and gray matter in various parts of the brain. Causality is unclear.
- 11/14 fMRI studies found no differences between groups based on cognitive measures, so based conclusions off of fMRI findings. The remaining three had methodological problems which could explain results (small sample sizes, age etc. differences between participants).
- Cocaine users have brain activation differences from nonusers, even after 25 days of abstinence. However, they do not show differences in task performance. These studies had methodological problems.
- Better controlled studies found that cocaine dependent participants had mild cognitive impairment and structural differences; however, this was less than the cognitive impairment of alcohol dependent participants. Structural differences were less than psychopathological disorders such as schizophrenia.
- My major uncertainties:
- To what extent are the impacts of cocaine use nonlinear? Almost all research is on human or animal subjects with exceptionally high dosage.
- If it is the case that moderate cocaine use causes, say, changes in gray matter volume in the basal ganglia, how likely is that change to be permanent?
- If moderate cocaine use causes, say, changes in gray matter volume in the basal ganglia, how likely is that change to be detrimental?
- How likely is oxidative stress to lead to neurotoxicity? Some research seems to assume they are synonymous, but this review thinks the first is a poor proxy for the second.