Effects of 2 mg/kg methylenedioxyethylamphetamine (MDE), 0.2 mg/kg psilocybin, 0.2 or 0.4 mg/kg methamphetamine and placebo on brain glucose metabolism were compared in a between-subjects study in 32 healthy volunteers (21 men, 11 women, average age 34.2, range 27-47). All volunteers were healthy as established by medical and psychiatric examination, and none reported major mental illness in themselves or in first-degree family members. MDE was administered to 8 of 32 individuals on two occasions. Participants performed a word association task in one session and a word repetition task in another session conducted two to four weeks later, and [F18]-fluorodeoxyglucose (FDG) PET scans, co-registered with MRI and recorded during peak drug effects, were performed to measure glucose metabolism during task performance. A study of the subjective, physiological and neuroendocrine effects of all three drugs was performed on the same sample and published within the same year (see Gouzoulis-Mayfrank, Thelen et al. 1999) State-Trait Anxiety Scale (STAI), Hallucinogen Rating Scale (HRS), Bech Rafaelsen Mania and Melancholia Scales, and the observer-scored positive and negative Syndrome Scale (PANSS) were used to assess subjective effects but not described here in detail. Brain glucose metabolism was compared using regions of interest (ROIs) and normalizing glucose metabolism for each region by relating it to global metabolism. MDE produced decreased metabolism in left precentral and right superior prefrontal areas, and a trend for reduced metabolism in other frontal areas save frontal operculum. Increased glucose metabolism was seen bilaterally in cerebellum. (By comparison, psilocybin was associated with increased metabolism in right anterior cingulate and frontal operculum and decreased metabolism in right thalamus, and methamphetamine produced bilateral increases in cerebellum and trend for decreased metabolism in right parietal and temporoparietal areas.) Decreased metabolism in left precentral area was associated with Ògeneral psychopathology,Ó as was decreased metabolism in frontal areas. Decreased metabolism in frontal regions was also associated with cognitive difficulties during the experience. Increased metabolism in the cerebellum was associated with cognitive problems, reduced sense of self-control or will (HRS ÒvolitionÓ), anxiety and depression score. Increased metabolism in the right anterior cingulate was associated with attentional deficits. (It should be noted that increased R anterior cingulate metabolism was correlated with anxiety in psilocybin condition). In people given MDE, the word association task was associated with increased metabolism in the left middle prefrontal and left superior temporal areas, and also right caudate (left frontal operculum in placebo). Decreased metabolism was seen in the right posterior cingulate. MDE produced moderately fewer word associations as compared with placebo controls, but this difference was not statistically significant, and none of the drugs produced any differences in facility in word repetition.

Comments:
Up to the current date (2003), this paper is one of two functional imaging studies of entactogens. The other is an PET study measuring cerebral blood flow with radiolabeled oxygen after MDMA. The two studies produce somewhat differing results, but it is difficult to compare findings. The other study is a within-subjects study, used a different imaging technique and examined a different entactogen. However, both studies found increased activity in the cerebellum and possibly cingulate. This study found decreased metabolism in the frontal area, whereas the other study found trends for increased metabolism in some prefrontal areas. Surprisingly, this study did not find any changes in amygdalar metabolism, while the other study found a decrease in regional cerebral blood flow (rCBF) in left amygdala, and less decrease in amygdala rCBF was associated with increased anxiety. It is unclear why imaging of cerebral blood flow, but not glucose metabolism, should be able to detect this change, but these differences may also relate to differences in study design. Findings from this study suggest that cerebellar activity may play a role in emotion and attention. This paper also attempts to compare functional imaging after three different drugs. It would appear from this study that like MDMA, MDE can be safely administered to humans.

[See also under psilocybin]