Brain research
March 27, 1995
S M Pearl, K Herrick-Davis, M Teitler et al.
78 citations
Noribogaine, a suspected metabolite of ibogaine, binds more strongly than ibogaine to all three types of opioid receptors. Ibogaine had highest affinity for kappa receptors, less for mu, and no measurable affinity for delta receptors. Noribogaine showed higher affinity for kappa, mu, and delta receptors, suggesting it is active in the body and may contribute to ibogaine's effects.
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.
Brain research
March 25, 1996
S D Glick, S M Pearl, J Cai et al.
63 citations
Ibogaine, a natural alkaloid, is claimed to reduce opioid and stimulant addiction for six months after a single dose, though it is eliminated from the body within hours. A metabolite, noribogaine, may explain this prolonged effect. In rats, a 40 mg/kg dose of noribogaine decreased morphine and cocaine self-administration, reduced morphine-induced locomotor stimulation, and lowered dopamine levels in the nucleus accumbens and striatum—effects similar to those of ibogaine at the same dose, but without ibogaine-like tremors. These findings suggest noribogaine mediates ibogaine's anti-addictive properties.
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.
Brain research
February 28, 1997
S D Glick, I M Maisonneuve, S M Pearl
38 citations
Ibogaine, a substance with potential anti-addictive properties, works through two brain receptor systems: kappa-opioid and NMDA. In rats, blocking kappa-opioid receptors and activating NMDA receptors together partially prevented ibogaine's ability to reduce morphine self-administration and to counteract morphine-induced hyperactivity. Either treatment alone, or in combination, also blocked ibogaine's effects on dopamine release and metabolism in the striatum. These results suggest that ibogaine's anti-addictive effects rely on both its kappa-opioid agonist and NMDA antagonist actions.
Psychopharmacology
October 1, 1995
S M Pearl, D W Johnson, S D Glick
31 citations
Prior morphine exposure enhances ibogaine's ability to reduce morphine-induced locomotor stimulation in female rats. Rats pretreated with morphine (10, 20, or 30 mg/kg) before receiving ibogaine (40 mg/kg) showed significantly less locomotor activity when later given morphine (5 mg/kg), compared to rats pretreated with saline. This effect occurred across a range of ibogaine (5–60 mg/kg) and morphine test (2.5–5 mg/kg) doses. Even low ibogaine doses (5 and 10 mg/kg) that alone had no effect became effective after morphine pretreatment. The findings suggest that an individual's history of opioid exposure may influence ibogaine's efficacy against opioid addiction.
Neuropharmacology
January 1, 1996
S M Pearl, I M Maisonneuve, S D Glick
16 citations
Prior morphine exposure enhances ibogaine's ability to block morphine-induced dopamine release in the striatum and nucleus accumbens of female rats. Neither morphine pretreatment, ibogaine alone, nor saline altered morphine-induced increases in extracellular dopamine or its metabolites. Only when morphine pretreatment was combined with ibogaine was the morphine-induced elevation of dopamine completely blocked, while metabolites remained unaffected. This suggests that prior drug exposure may influence ibogaine's effectiveness in treating opioid addiction.