Life sciences
January 1, 1996
L B Hough, S M Pearl, S D Glick
72 citations
Ibogaine, a substance being studied for anti-addictive properties, was measured in rats' plasma, brain, kidney, liver, and fat after injection into the abdomen or under the skin. One hour after a 40 mg/kg dose into the abdomen, drug levels ranged from 106 ng/ml in plasma to 11,308 ng/g in fat, with higher levels after injection under the skin. Levels dropped 10-20 fold after 12 hours. The results indicate that ibogaine undergoes a substantial first-pass effect when given into the abdomen, accumulates heavily in fat due to its lipophilic nature, and its persistence in fat may contribute to a long duration of action.
Pharmacology, biochemistry, and behavior
August 1, 1997
S M Pearl, L B Hough, D L Boyd et al.
58 citations
Ibogaine, a substance studied for antiaddictive properties, produces stronger behavioral effects in female rats than in males, correlating with higher ibogaine levels in their brains and plasma. Five hours after a 40 mg/kg dose, ibogaine antagonized morphine-induced locomotor activity only in females. At 19 hours after 10-60 mg/kg ibogaine or one hour after 5-40 mg/kg noribogaine (a metabolite), antagonism was greater in females. Brain and plasma levels of ibogaine and noribogaine were higher in females given the same dose. Levels were much lower at 19 hours than earlier, unlike a prior human study. Subcutaneous injection produced greater antagonism than intraperitoneal, consistent with higher brain levels. Sex differences likely stem from lower ibogaine bioavailability in males.
Biochemical pharmacology
January 6, 1995
C A Gallagher, L B Hough, S M Keefner et al.
32 citations
A new chemical method to measure the alkaloid ibogaine in biological samples uses extraction, derivatization, and gas chromatography-mass spectrometry, with a deuterated internal standard. Standard curves for ibogaine (50-400 ng) were linear. The detection limit is about 20 ng/mL of tissue extract (180 ng/g tissue), with a coefficient of variation of 8 to 12.5%. Aqueous ibogaine solutions (1-10 mg/mL) stored at 10°C for up to 7 months showed no more than 10% loss. Measuring brain ibogaine in rats 1 and 19 hours after a 40 mg/kg dose suggests rapid drug disappearance. The method will help reveal ibogaine's pharmacokinetic properties.
Brain research
November 25, 1996
A A Bagal, L B Hough, J W Nalwalk et al.
23 citations
Ibogaine, a putative anti-addictive agent, and its active metabolite noribogaine modulate morphine's pain-killing (antinociceptive) effects in rats, depending on timing and dose. When given 19 hours before morphine, ibogaine significantly reduced morphine's antinociception, but had no effect alone. In contrast, co-administration of ibogaine (1-40 mg/kg) with morphine increased antinociception in a dose-dependent manner. Co-administration of noribogaine (40 mg/kg) with morphine also enhanced antinociception, while noribogaine pretreatment (19 hours) had no effect. The findings indicate that ibogaine acutely potentiates morphine antinociception, likely through noribogaine, but the delayed inhibitory effect after 19 hours is not explained by noribogaine.
Brain research
August 14, 1992
S D Glick, C A Gallagher, L B Hough et al.
21 citations
Ibogaine pretreatment in rats did not alter brain morphine levels at 30 minutes or 2 hours after injection, but it significantly increased brain amphetamine levels at both time points, with a greater increase at 2 hours. These findings suggest that ibogaine irreversibly inhibits an enzyme that metabolizes amphetamine, indicating that the functional interactions between ibogaine and amphetamine, unlike those with morphine, may stem from a drug-drug interaction in the liver.
Methods and findings in experimental and clinical pharmacology
March 1, 2000
L B Hough, A A Bagal, S D Glick
7 citations
After a 20 mg/kg intravenous infusion in rats, ibogaine levels in plasma declined rapidly in a two-phase pattern, with an initial half-life of 7.3 minutes and a terminal half-life of 3.3 hours. Drug clearance was 5.9 L/h. Three hours after infusion, ibogaine concentrations in brain, liver, and kidney were 143–170 ng/g, but in adipose tissue the concentration was much higher at 3,328 ng/g. This sequestration in fat likely causes the drug to persist in the body longer than the terminal half-life suggests. The initial rapid disappearance from plasma may result from metabolic demethylation and redistribution to tissues.