BilZ0r
Bluelight Crew
- Joined
- Dec 15, 2003
- Messages
- 6,675
Ibogaine has always been a drug that has scared me. Its pharmacology seems exessively complex, its politics are heady and its uses are divergent.
One thing about it, that doesn't seem to get to much press, are repeated claims of cerebelar neurotoxicity (O'Hearn et al., 1993, Molinari et al., 1996). Even the neurotoxicity seems unreasonabley complicated. Firstly, it is expressed rats and not mice (Scallet et al., 1996). The neurotoxicity is dependent on long distances glutamatergic projections from the inferior olive which fire densly onto cerebellar Purkinje cells, as ablation of the inferior olive is neuroprotectant against ibogaine neurotoxicity (O'Hearn and Molliver, 1997). Finally, even though signs point to excitotoxicity, ibogaine-induced neurotoxic is excacerbated by ionotropic glutamate receptor antagonists (GKYI-52466, non-NMDA-antagonist) (O'Hearn and Molliver, 2004).
The important question is however, is neurotoxicity a problem for humans. Well at current standing its quite hard to comment. As the neurotoxicity isn't conserved across rodents, it's hard to know whether it will be conserved to primates, but perhaps we should look at doses first. A nice dose responce study By Xu et al., 2000 showed that all rats given over 75mg/kg ibogaine showed neurotoxicty, while 2 out of 6 rats on 50mg/kg showed neurotoxicity, and 25mg/kg was non-toxic. Molinari et al., 1996 showed neurotoxiciyt at 100mg/kg but none at 40mg/kg. So we can assume neurotoxicity starts at 41-50mg/kg (all I.P). We need to convert these results to plasma concentrations to compare these to human dosages. From the results of Zubran et al., 1999 we can see a relationship of IP dose to plasma concentration of [PLASMA](ng/mL) = 30.39 x IP DOSE (mg/kg) r-squared>0.98. Hence the neurotoxic thershold in rats is 1246-1519ng/mL.
Mash et al., 1998 report two cases of males receving 800mg and 1000mg orally, who reached peak plasma concentrations of 600 and 1250ng/mL respectively. These results indicated that doses of >1000mg may reach into the plasma range of neurotoxic doses in rats.
The doses required for anit-addictive actions are said to be in the 10mg/kg, ~700mg range (Ibogaine.co.uk) though some reports suggest doses of over 1000mg are needed (Sheppard, 1994).
Because of the ambiguity of intra-species scaling, intra-species effects and the unknown dosage of anti-addictive effects, conclusions as to whether ibogaine may be neurotoxic to humans are hard to make, yet data indicates that users should be wary about neurotoxic effects of higher doses.
On an unrelated note, I found a very interesting article claiming that the anti-addictive actions of Ibogaine in alcohol addiction are mediated by neurotrophic factors, specifically GDNF (He et al., 2005)
One thing about it, that doesn't seem to get to much press, are repeated claims of cerebelar neurotoxicity (O'Hearn et al., 1993, Molinari et al., 1996). Even the neurotoxicity seems unreasonabley complicated. Firstly, it is expressed rats and not mice (Scallet et al., 1996). The neurotoxicity is dependent on long distances glutamatergic projections from the inferior olive which fire densly onto cerebellar Purkinje cells, as ablation of the inferior olive is neuroprotectant against ibogaine neurotoxicity (O'Hearn and Molliver, 1997). Finally, even though signs point to excitotoxicity, ibogaine-induced neurotoxic is excacerbated by ionotropic glutamate receptor antagonists (GKYI-52466, non-NMDA-antagonist) (O'Hearn and Molliver, 2004).
The important question is however, is neurotoxicity a problem for humans. Well at current standing its quite hard to comment. As the neurotoxicity isn't conserved across rodents, it's hard to know whether it will be conserved to primates, but perhaps we should look at doses first. A nice dose responce study By Xu et al., 2000 showed that all rats given over 75mg/kg ibogaine showed neurotoxicty, while 2 out of 6 rats on 50mg/kg showed neurotoxicity, and 25mg/kg was non-toxic. Molinari et al., 1996 showed neurotoxiciyt at 100mg/kg but none at 40mg/kg. So we can assume neurotoxicity starts at 41-50mg/kg (all I.P). We need to convert these results to plasma concentrations to compare these to human dosages. From the results of Zubran et al., 1999 we can see a relationship of IP dose to plasma concentration of [PLASMA](ng/mL) = 30.39 x IP DOSE (mg/kg) r-squared>0.98. Hence the neurotoxic thershold in rats is 1246-1519ng/mL.
Mash et al., 1998 report two cases of males receving 800mg and 1000mg orally, who reached peak plasma concentrations of 600 and 1250ng/mL respectively. These results indicated that doses of >1000mg may reach into the plasma range of neurotoxic doses in rats.
The doses required for anit-addictive actions are said to be in the 10mg/kg, ~700mg range (Ibogaine.co.uk) though some reports suggest doses of over 1000mg are needed (Sheppard, 1994).
Because of the ambiguity of intra-species scaling, intra-species effects and the unknown dosage of anti-addictive effects, conclusions as to whether ibogaine may be neurotoxic to humans are hard to make, yet data indicates that users should be wary about neurotoxic effects of higher doses.
On an unrelated note, I found a very interesting article claiming that the anti-addictive actions of Ibogaine in alcohol addiction are mediated by neurotrophic factors, specifically GDNF (He et al., 2005)
