- To date, there are no objective, reliable biomarkers of cannabis intoxication
- In a double-blind, placebo-controlled, crossover study, functional near-infrared spectroscopy was used to examine the effect of tetrahydrocannabinol (THC) on the hemodynamic response in the prefrontal cortex (PFC) during a working memory task
- In 54 participants, THC-induced intoxication caused significantly greater activation of the PFC than placebo. THC at similar doses not associated with significant intoxication did not cause activation of the PFC
- This study reveals the potential of using fNIRS to measure cannabis intoxication objectively
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Tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, remains in urine and blood for weeks after last use. Law enforcement officers and others can't use it as a biomarker of cannabis intoxication because a test for THC metabolites in body fluids is positive long after the period of intoxication is over.
Many of the impairments that can be associated with cannabis use—memory, attention, reaction time, visual tracking and motor function—rely on activity in the prefrontal cortex (PFC). Researchers at Massachusetts General Hospital have therefore been investigating whether measurement of PFC activity can detect cannabis intoxication.
In a previous study, Jodi M. Gilman, PhD, director of neuroscience in the Center for Addiction Medicine (CAM) at Mass General, and colleagues found that in regular cannabis users who became intoxicated after a single dose of THC, there was significant increased PFC activity.
In NeuroImage, Dr. Gilman, and CAM founding director A. Eden Evins, MD, MPH, and colleagues extend these findings, reporting the first double-blind, placebo-controlled crossover study to show that PFC activation can serve as a biomarker of cannabis intoxication.
In both this study and the earlier one, the researchers measured PFC activity with functional near-infrared spectroscopy (fNIRS). This noninvasive brain imaging technique can be used outside a laboratory at relatively low cost. A cap containing fNIRS optodes is placed on the head of the person being tested, and light is projected onto the forehead (the site of the PFC).
fNIRS capitalizes on the differences in the light absorption spectra of oxygenated and deoxygenated hemoglobin to detect brain activity. Brain activity is associated with changes in oxygenated and deoxygenated hemoglobin concentrations.
The researchers recruited 54 adults from the community, ages 18 to 55, who reported at least weekly cannabis use.
Each participant came for two study visits at least seven days apart. In randomized order, they received placebo at one visit and between 5 and 50 mg of dronabinol (a synthetic form of THC) at the other. They rated the effects of the drug at baseline and about every 15 minutes for four hours.
At each of the two study visits, participants underwent fNIRS before drug administration (pre-scan), about 100 minutes after administration (peak scan, corresponding to the expected time of the peak effect of dronabinol) and about 200 minutes after administration (post-scan). During each scan, participants completed a working memory task.
- Twenty-seven participants (50%) were considered high responders to THC, with an increase in intoxication ratings of 68% during the study period. In the low responder group, the increase was only 16%
- Only participants who reported greater increases in intoxication showed greater deterioration in performance on the memory task
- In high responders, the concentration of oxygenated hemoglobin on the peak scan was significantly increased throughout the PFC, compared with the pre-scan. The concentration decreased between the peak scan and the post-scan when intoxication had mostly resolved
- After placebo, or after receiving THC but not experiencing intoxication, participants did not show either worsening cognitive performance or an increased concentration of oxygenated hemoglobin in the PFC
In short, THC intoxication caused increased PFC activity, and fNIRS was able to measure that effect.
More than 20 years ago, research with positron emission tomography also demonstrated increases in cortical activation following cannabis smoking or infusion of THC, which lends credence to these results. However, in the current study, it isn't certain that the changes in fNIRS were associated with THC specifically, not some other form of intoxication.
Therefore, the researchers plan to test how combinations of drugs that are commonly used together, such as THC and alcohol or opiates, affect PFC activation.
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