AimThe stimulating herbal drug khat is habitually used in East Africa and the Arabian peninsula but is also imported into other countries. The aim was to study the pharmacokinetics of its alkaloids cathinone, cathine and norephedrine. Methods Four volunteers chewed khat leaves in an amount equivalent to onequarter of that used in a typical khat session. Blood samples were collected up to 80 h and the alkaloids were assayed using gas chromatography-mass spectrometry. The data were evaluated using computerized pharmacokinetic compartmental analysis. Results The plasma concentration-time data for the alkaloids could be described using a two-compartment model with two-segment absorption. The mucosa of the oral cavity is considered to be the first absorption segment, where the major proportion of the alkaloids is absorbed (mean ± SD 59 ± 21% for cathinone and 84 ± 6% for cathine). The extraction of the alkaloids from the leaves by chewing was very effective with only 9.1 ± 4.2% remaining as a residue. Cathinone was eliminated from the central compartment with a mean half-life of 1.5 ± 0.8 h. The half-life of cathine was 5.2 ± 3.4 h. The metabolism of cathinone to norephedrine had a substantial influence on its plasma concentration profile. Psychophysical functions were essentially unaffected by the chewing of khat. Conclusions The pharmacokinetics of khat alkaloids in humans explain why chewing is the preferred form of khat ingestion. Subjects absorbed a mean dose of 45 mg of cathinone, and did not suffer any severe adverse reactions.

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Diffuse axonal injury (DAI) is considered to be the morphological correlate of traumatic brain injury as seen in acceleration/deceleration trauma and is believed to be the main cause for a poor clinical outcome in the absence of detectable intracranial lesions. To estimate the overall incidence of DAI, and since most changes are only seen microscopically to rule out whether there is a high number of undetected cases, 450 non-selected human brains were examined. Samples from two brain areas (pons and cerebrum) were immunostained for beta-amyloid-precursor-protein (betaAPP), and axonal damage was assessed microscopically. Axonal injury was detected in 12% of all cases, but only one third had a history of traumatic brain injury. The majority of the positive cases were associated with drug intoxication, chiefly due to opiates. betaAPP staining was positive in both pons and cerebrum to a much higher extent in intoxication than in trauma cases; the latter showing axonal damage mainly in the pons area. This may reflect a more generalized pathomechanism in the intoxication group as compared to more biomechanical mechanisms in the trauma group. The findings also show that various causes may produce diffuse axonal injury and suggest that traumatic brain injury is not the only and probably not even the main cause of the observed neuropathological changes. A correlation between axonal damage and age-related processes could not be shown.

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