Ibogaine HCl

The ibogaine used in this study was chemically synthesized using voacangine as starting material, which was extracted from the root bark of Voacanga africana (purchased from CAPE LABS) using a modification of a previously described procedure (Jenks, 2002). Briefly, 100g of grounded root bark of V. africana was extracted with a 1% aqueous solution of HCl (6 × 500 mL). The combined aqueous extracts were basified by adding concentrated NH₄OH until pH 10–11. A brown precipitate was separated by centrifugation and dried at 60°C for 24 h. This solid was taken in acetone and filtered to discard root impurities. The solvent was evaporated in vacuo to afford a total alkaloid extract of 3.5–4.0 g. Column chromatography (SiO₂, Hex:EtOAc:NH₄OH, 90:10:0.01) allowed to obtain 1g of pure voacangine which was analyzed by ¹H and ¹³C NMR (See Supplementary Material). Voacangine was decarboxylated as follows. To a solution of voacangine in EtOH (0.45 M) in a double necked round bottomed flask, KOH in pellets (5 equivalents) was added. The solution was heated to reflux until consumption of the starting material was evident by thin layer chromatography (TLC) analysis. EtOH was removed under reduced pressure, and the residue was dissolved at 0°C in a round bottomed flask using a 6% (v/v) aqueous solution of HCl (enough quantity to adjust pH to 1). The system was then heated to reflux for 5 min. Once the starting material consumption was evident by TLC analysis, the solution was carefully basified using 50% NaOH (pH 10–11). Precipitation of ibogaine as a white solid was observed. Ethyl acetate was added, and the resultant biphasic system was transferred into a separation funnel. The aqueous phase was extracted three times with EtOAc. The combined organic layers were dried under Na₂SO₄, and the solvent was removed in vacuo. Purification was carried out using column chromatography purification (SiO₂, hexanes: ethyl acetate 8:2 + 0.5% ammonium hydroxide). Ibogaine free base was obtained with an 86% and was analyzed by ¹H and ¹³C NMR (see Supplementary Material). Crystallization from EtOH afforded a crystalline solid which was converted to the corresponding hydrochloride by treatment with diethyl ether saturated with HCl(g). Purity of ibogaine⋅HCl was determined by GC-MS analysis as 98.3% (see Supplementary Material). Dissolution of ibogaine-HCl to prepare the samples for i.p. injection was carried out using warm saline that was previously degassed by nitrogen bubbling.