ABSTRACT
Ibogaine is a naturally occurring substance which has been increasingly used in the lay-scene to reduce craving and relapse in patients with substance use disorders (SUDs). Although human clinical trials on the safety and efficacy of ibogaine are lacking, animal studies do support the efficacy of ibogaine. In this systematic review and meta-analysis (MA), we summarise these animal findings, addressing three questions: (1) does ibogaine reduce addictive behaviour in animal models of SUDs?; (2) what are the toxic effects of ibogaine on motor functioning, cerebellum and heart rhythm?; (3) what are neuropharmacological working mechanisms of ibogaine treatment in animal models of SUDs? MA of 27 studies showed that ibogaine reduced drug self-administration, particularly during the first 24 h after administration. Ibogaine had no effect on drug-induced conditioned place preference. Ibogaine administration resulted in motor impairment in the first 24 h after supplementation, and cerebral cell loss even weeks after administration. Data on ibogaines effect on cardiac rhythm, as well as on its neuropharmacological working mechanisms are limited. Our results warrant further studies into the clinical efficacy of ibogaine in SUD patients in reducing craving and substance use, but close monitoring of the patients is recommended because of the possible toxic effects. In addition, more work is needed to unravel the neuropharmacological working mechanisms of ibogaine and to investigate its effects on heart rhythm.
Subject(s)
Disease Models, Animal , Ibogaine/pharmacology , Illicit Drugs , Substance-Related Disorders/rehabilitation , Animals , Cerebellum/drug effects , Dose-Response Relationship, Drug , Female , Ibogaine/toxicity , Male , Motor Activity/drug effects , Neurons/drug effects , Self AdministrationABSTRACT
In this study, five different oil based adjuvants were compared to assess efficacy and side effects. Mice were injected subcutaneously (s.c.) or intraperitoneally (i.p.) with a weak immunogen (synthetic peptide) emulsified in Freund's adjuvant (FA), Specol, RIBI, TiterMax or Montanide ISA50. Efficacy of adjuvants was evaluated based on their properties to induce peptide specific IgG1, IgG2a and total IgG antibodies, native protein cross-reactive antibodies and cytokine production. Side effects were evaluated based on clinical and behavioural abnormalities, and (histo)pathological changes. Although marked differences in isotype profile and height of titre are observed among the different adjuvants used, we found that FA, Montanide ISA50 and Specol worked equally well in the s.c. and i.p. route, TiterMax functioned only when given i.p. and RIBI also did not perform up to par. The number of cytokine (interferon-gamma and interleukin-4) producing spleen cells was significantly higher after injection of RIBI compared with other adjuvants. Injection of FA or TiterMax resulted in severe pathological changes while after RIBI injection minimal changes were observed. In conclusion, high peptide specific antibody levels with limited side effects can be obtained by s.c. injection of peptide combined with Montanide ISA50 or Specol as alternatives to FA.
Subject(s)
Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/toxicity , Adjuvants, Immunologic/administration & dosage , Animals , Antibody Specificity , Cell Wall Skeleton/administration & dosage , Cell Wall Skeleton/pharmacology , Cell Wall Skeleton/toxicity , Cord Factors/administration & dosage , Cord Factors/pharmacology , Cord Factors/toxicity , Cross Reactions , Cytokines/biosynthesis , Emulsions , Female , Freund's Adjuvant/administration & dosage , Freund's Adjuvant/pharmacology , Freund's Adjuvant/toxicity , Hydrocarbons/administration & dosage , Hydrocarbons/pharmacology , Hydrocarbons/toxicity , Immunoglobulin G/biosynthesis , Injections, Intraperitoneal , Injections, Subcutaneous , Lipid A/administration & dosage , Lipid A/analogs & derivatives , Lipid A/pharmacology , Lipid A/toxicity , Mannitol/administration & dosage , Mannitol/analogs & derivatives , Mannitol/pharmacology , Mannitol/toxicity , Mice , Mice, Inbred BALB C , Mineral Oil/administration & dosage , Mineral Oil/pharmacology , Mineral Oil/toxicity , Oils , Oleic Acids/administration & dosage , Oleic Acids/pharmacology , Oleic Acids/toxicity , Peptides/immunology , Poloxalene/administration & dosage , Poloxalene/pharmacology , Poloxalene/toxicity , Polysorbates/administration & dosage , Polysorbates/pharmacology , Polysorbates/toxicity , Spleen/cytology , Spleen/immunologyABSTRACT
Sixteen 15 kg liveweight entire-male pigs were given either a low-fibre (1.21 g/100 g Neutral detergent fibre, NDF) or a high-fibre (6.38 g 100 g, NDF) wheat bread as their sole source of dietary protein, in a conventional 21-day metabolism study. A glucose/oil supplement which was assumed to be completely absorbed was given with the bread to ensure a high ratio of dietary energy to protein, to allow measurement of biological value (BV). The apparent faecal digestibility of gross energy was significantly (p < 0.001) lower (7.4% units) for pigs given the high-fibre bread as was the apparent digestibility of NDF (24% units lower). The apparent faecal digestibility of total nitrogen was also significantly (p < 0.001) lower for the animals fed the high-fibre bread, but there were no significant differences between the breads for the BV of their protein. The overall mean BV for the breads was 46%. The results indicate a significantly lower digestibility of nutrients and gross energy in breads containing appreciable quantities of wheat bran fibre.